79200-56-9

Basic information

• Product Name: ((1R,4S)-2-Azabicyclo[2.2.1]hept-5-en-3-one
• Synonyms: (1R)-(-)-2-AZABICYCLO[2.2.1]HEPT-5-EN-3-ONE;(1R,4S)-2-AZA-BICYCLO[2.2.1]HEPT-5-EN-3-ONE;(-)-VINCE'S LACTAM;(1R)-(-)-2-AZABICYCLO(2.2.1)HEPT-5-EN-3- ONE, 98+% (99% EE/HPLC);(-)-Vince lactam;(1R)-(-)-2-Azabicyclo[2.2.1]hept-5-en-3-one,98%,> 95%ee;(-)-2-Azabicyclo[2.2.1]hept-5-en-3-one, > 95% ee;(1R)-(-)-2-Azabicyclo[2.2.1]hept-5-en-3-one ,98%
• CAS NO: 79200-56-9
• Molecular Formula: C₆H₇NO
• Molecular Weight: 109.13
• EINECS: 418-530-1
• Product Categories: Antiviral Agents;Chiral Building Blocks;Lactams;Organic Building Blocks;Chiral Reagents;Heterocycles;Intermediates;Heterocycle-other series
• Mol File: 79200-56-9.mol
• Article Data: 20

Chemical Properties

• Melting Point: 94-97 °C(lit.)
• Boiling Point: 319.302 °C at 760 mmHg
• Flash Point: 167.131 °C
• Appearance: Off-white to beige/Crystals or Crystalline Powder
• Density: 1.198 g/cm³
• Vapor Pressure: 0.000342mmHg at 25°C
• Refractive Index: 1.545
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly, Heated), DMSO (Slightly), Methanol (Slightly)
• PKA: 15.48±0.20(Predicted)
• BRN: 4230721
• CAS DataBase Reference: ((1R,4S)-2-Azabicyclo[2.2.1]hept-5-en-3-one(CAS DataBase Reference)
• NIST Chemistry Reference: ((1R,4S)-2-Azabicyclo[2.2.1]hept-5-en-3-one(79200-56-9)
• EPA Substance Registry System: ((1R,4S)-2-Azabicyclo[2.2.1]hept-5-en-3-one(79200-56-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22-41-43
• Safety Statements: 24-26-37/39
• WGK Germany: 1
• Hazardous Substances Data: 79200-56-9(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 79200-56-9 differently. You can refer to the following data:
1. ((1R,4S)-2-Azabicyclo[2.2.1]hept-5-en-3-one is an abacavir intermediate. It is used as an intermediate in the synthesis of carbocyclic sugar amines, carbanucleosides, and carbocyclic dinucleotide analogues.
2. (1R)-(-)-2-Azabicyclo[2.2.1]hept-5-en-3-one can be used as a precursor to prepare: Amino-peramivir, a potent neuraminidase inhibitor.Five membered analogs of 4-amino-5-halopentanoic acids as potential GABA aminotransferase (GABA-AT) inactivators.

General Description

(1R)-(-)-2-Azabicyclo[2.2.1]hept-5-en-3-one is a bicyclic γ-lactam.

InChI:InChI=1/C6H7NO/c8-6-4-1-2-5(3-4)7-6/h1-2,4-5H,3H2,(H,7,8)/t4-,5+/m1/s1

Synthetic route

(1R,4S)-N-hydroxymethyl-2-azabicyclo<2.2.1>hept-5-en-3-one (157810-21-4) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
With methanol; ammonium hydroxide for 13h; Ambient temperature;	51%
With ammonium hydroxide In methanol for 12h; Ambient temperature;	51%

racemic 2-azabicyclo[2.2.1]hept-5-en-3-one (49805-30-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + (1R,4S)-4-aminocyclopenten-2-ene-1-carboxylic acid (134003-04-6)

Conditions	Yield
With (+)-γ-lactamase from Bradyrhizobium japonicum USDA 6 In aq. buffer at 45℃; for 1h; pH=8; Catalytic behavior; Temperature; pH-value; Resolution of racemate; Enzymatic reaction; enantioselective reaction;	A 49.9% B n/a
With cloned (+)-γ-lactamase at 25℃; for 1h; pH=7.5; Ring cleavage;

racemic 2-azabicyclo[2.2.1]hept-5-en-3-one (49805-30-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
With A. viscous (NCIM No.2451) In phosphate buffer for 21h; pH=7.5;	31.2%
With Penicillium thomi AM91 for 48h; Reagent/catalyst; Enzymatic reaction;	n/a

2-azabicyclo[2.2.1.]hept-5-en-3-one (49805-30-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

(1R,4S)-2-(p-Methoxybenzyl)-2-azabicyclo<2.2.1>-5-hepten-3-one (168960-17-6) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
With ammonium cerium(IV) nitrate In water; acetonitrile at 0℃; for 0.283333h; Yield given;

2-azabicyclo[2.2.1.]hept-5-en-3-one (49805-30-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
With brucine In methanol at 20℃; for 6h;
With Methylobacterium sp. Y1-6 at 30℃; for 24h; Overall yield = 19 %Chromat.;	A n/a B n/a
With malonamidase E2 (MAE2) In aq. phosphate buffer at 30℃; for 24h; pH=7.5; Resolution of racemate; Enzymatic reaction;	A n/a B n/a
With Cu-(R)-2,2'-dihydroxy-1,1'-binaphthalene-6,6'-dicarboxylic acid organic framework silica composite In ethanol; hexane Resolution of racemate;

2-azabicyclo[2.2.1.]hept-5-en-3-one (49805-30-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + (1R,4S)-4-aminocyclopenten-2-ene-1-carboxylic acid (134003-04-6)

Conditions	Yield
With lactamase Enzymatic reaction;
With Bradyrhizobium japonicum USDA 6 (+)-γ-lactamase In aq. buffer at 50℃; pH=6; Enzymatic reaction; enantioselective reaction;	A n/a B n/a

2-hydroxymethyl-2-azabicyclo<2.2.1>hept-5-en-3-one (157732-10-0) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 43 percent / various solvent(s) / 0.5 h / Ambient temperature; immobilized lipase PS on diatomite 2: 90 percent / H2O / diisopropyl ether / 3 h / Ambient temperature; lipase PS 3: 51 percent / aq. NH3 / methanol / 12 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 2: 51 percent / Nh4OH, MeOH / 13 h / Ambient temperature View Scheme

N-acetoxymethyl-2-azabicyclo[2.2.1]hept-5-en-3-one (183074-62-6) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 41 percent / H2O / diisopropyl ether / 3 h / Ambient temperature; lipase PS 2: 51 percent / aq. NH3 / methanol / 12 h / Ambient temperature View Scheme

(1R,4S)-N-acetoxymethyl-2-azabicyclo[2.2.1]hept-5-en-3-one (157732-11-1) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / H2O / diisopropyl ether / 3 h / Ambient temperature; lipase PS 2: 51 percent / aq. NH3 / methanol / 12 h / Ambient temperature View Scheme

(1R,4S,6S)-6-(tert-Butyldimethylsiloxy)-2-azabicyclo<2.2.1>-3-heptanone (168773-48-6) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 4: 98 percent / DBU / xylene / 16.5 h / Heating 5: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 4: 20 percent 5: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 6: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 4: 40 percent / LiHMDS 5: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 6: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(1R,4S,6R)-6-Iodo-2-(p-methoxybenzyl)-2-azabicyclo<2.2.1>-3-heptanone (168773-56-6) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / DBU / xylene / 16.5 h / Heating 2: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(1R,4S,6S)-6-Hydroxy-2-(p-methoxybenzyl)-2-azabicyclo<2.2.1>-3-heptanone (168773-55-5) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 2: 98 percent / DBU / xylene / 16.5 h / Heating 3: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 2: 20 percent 3: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 4: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 2: 40 percent / LiHMDS 3: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 4: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(1R,4S)-2-(p-Methoxybenzyl)-2-azabicylo<2.2.1>heptane-3,6-dione (168773-57-7) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 20 percent 2: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 3: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: 40 percent / LiHMDS 2: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 3: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(1R,4S,6S)-6-(tert-Butyldimethylsiloxy)-2-benzyl-2-azabicyclo<2.2.1>-3-heptanone (168773-42-0) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 6 steps 1: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 2: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 5: 98 percent / DBU / xylene / 16.5 h / Heating 6: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 2: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 5: 20 percent 6: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 7: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 2: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 5: 40 percent / LiHMDS 6: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 7: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(5S,6R)-1-Benzyl-5-<(tert-butyldimethylsilyl)oxy>-6-(bromomethyl)-2-piperidinone (168773-45-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 7 steps 1: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 3: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 6: 98 percent / DBU / xylene / 16.5 h / Heating 7: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 8 steps 1: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 3: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 6: 20 percent 7: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 8: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 8 steps 1: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 3: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 6: 40 percent / LiHMDS 7: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 8: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(5S,6R)-1-Benzyl-5-<(tert-butyldimethylsilyl)oxy>-6-(hydroxymethyl)-2-piperidinone (168773-41-9) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 8 steps 1: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 2: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 4: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 7: 98 percent / DBU / xylene / 16.5 h / Heating 8: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 9 steps 1: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 2: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 4: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 7: 20 percent 8: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 9: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 9 steps 1: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 2: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 4: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 5: 97 percent / TBAF / tetrahydrofuran / 0.33 h 6: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 7: 40 percent / LiHMDS 8: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 9: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(1R,4S,6S)-6-(tert-Butyldimethylsiloxy)-2-(p-methoxybenzyl)-2-azabicyclo<2.2.1>-3-heptanone (168773-47-5) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 97 percent / TBAF / tetrahydrofuran / 0.33 h 2: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 3: 98 percent / DBU / xylene / 16.5 h / Heating 4: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: 97 percent / TBAF / tetrahydrofuran / 0.33 h 2: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 3: 20 percent 4: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 5: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: 97 percent / TBAF / tetrahydrofuran / 0.33 h 2: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 3: 40 percent / LiHMDS 4: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 5: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(5S,6R)-1-(p-Methoxybenzyl)-5-<(tert-butyldimethylsilyl)oxy>-6-(hydroxymethyl)-2-piperidinone (168773-44-2) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 6 steps 1: 89 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 2: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 5: 98 percent / DBU / xylene / 16.5 h / Heating 6: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1: 89 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 2: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 5: 20 percent 6: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 7: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1: 89 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 2: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 3: 97 percent / TBAF / tetrahydrofuran / 0.33 h 4: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 5: 40 percent / LiHMDS 6: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 7: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(5S,6R)-1-(p-Methoxybenzyl)-5-<(tert-butyldimethylsilyl)oxy>-6-(bromomethyl)-2-piperidinone (168773-46-4) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 4: 98 percent / DBU / xylene / 16.5 h / Heating 5: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 4: 20 percent 5: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 6: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 2: 97 percent / TBAF / tetrahydrofuran / 0.33 h 3: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 4: 40 percent / LiHMDS 5: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 6: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(5S,6R)-1-Benzyl-5-<(tert-butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone (168773-40-8) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 9 steps 1: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 2: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 3: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 5: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 8: 98 percent / DBU / xylene / 16.5 h / Heating 9: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 10 steps 1: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 2: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 3: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 5: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 8: 20 percent 9: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 10: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 10 steps 1: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 2: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 3: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 5: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 6: 97 percent / TBAF / tetrahydrofuran / 0.33 h 7: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 8: 40 percent / LiHMDS 9: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 10: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

Trifluoro-methanesulfonic acid (1R,4S)-2-(4-methoxy-benzyl)-3-oxo-2-aza-bicyclo[2.2.1]hept-5-en-6-yl ester (168773-58-8) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 2: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(5S,6R)-1-(p-Methoxybenzyl)-5-<(tert-butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone (168773-43-1) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 7 steps 1: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 2: 89 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 3: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 6: 98 percent / DBU / xylene / 16.5 h / Heating 7: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 8 steps 1: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 2: 89 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 3: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 6: 20 percent 7: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 8: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 8 steps 1: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 2: 89 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 22 h 3: 90 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 4: 97 percent / TBAF / tetrahydrofuran / 0.33 h 5: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 6: 40 percent / LiHMDS 7: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 8: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(6R)-5-Hydroxy-6-<(benzyloxy)methyl>-2-piperidinone → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 11 steps 1: imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 10: 98 percent / DBU / xylene / 16.5 h / Heating 11: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 12 steps 1: imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 10: 20 percent 11: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 12: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 12 steps 1: imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 10: 40 percent / LiHMDS 11: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 12: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(5S,6R)-5-Hydroxy-6-<(benzyloxy)methyl>-2-piperidinone (168773-36-2) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 11 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 10: 98 percent / DBU / xylene / 16.5 h / Heating 11: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 12 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 10: 20 percent 11: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 12: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 12 steps 1: 92 percent / imidazole / dimethylformamide / 15 h 2: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 3: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 4: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 5: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 6: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 7: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 8: 97 percent / TBAF / tetrahydrofuran / 0.33 h 9: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 10: 40 percent / LiHMDS 11: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 12: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(5S,6R)-5-<(tert-Butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone (168773-38-4) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

Conditions	Yield
Multi-step reaction with 10 steps 1: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 2: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 3: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 4: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 6: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 7: 97 percent / TBAF / tetrahydrofuran / 0.33 h 8: 97 percent / PPh3, imidazole, I2 / toluene / 1.) 60 deg C, 10 min, 2.) reflux, 3.75 h 9: 98 percent / DBU / xylene / 16.5 h / Heating 10: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 11 steps 1: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 2: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 3: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 4: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 6: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 7: 97 percent / TBAF / tetrahydrofuran / 0.33 h 8: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 9: 20 percent 10: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 11: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme
Multi-step reaction with 11 steps 1: 99 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 42 h 2: 100 percent / H2 / 10percent Pd/C / ethanol / 23 h 3: 93 percent / CBr4, PPh3 / CH2Cl2 / 1.) 0 deg C to r.t., 1 h, 2.) r.t., 13 h 4: 99 percent / KHMDS / tetrahydrofuran / 1.) -50 to -35 deg C, 15 min, 2.) -35 deg C, 40 min 5: 99 percent / NH3, Na, t-BuOH / tetrahydrofuran / 1.) -78 deg C, 6 min, 2.) -78 to -33 deg C, 2 min 6: 90 percent / NaH, TBAI / tetrahydrofuran / 1.) 15 min, 2.) 21 h 7: 97 percent / TBAF / tetrahydrofuran / 0.33 h 8: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C to r.t., 20 min; r.t., 40 min 9: 40 percent / LiHMDS 10: 39 percent / HCO2H, Bu3N / PPh3, Pd(OAc)2 / dimethylformamide / 6 h 11: CAN / acetonitrile; H2O / 0.28 h / 0 °C View Scheme

(–)-methyl (1S,4R)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride (229613-83-6) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9)

2-azabicyclo[2.2.1.]hept-5-en-3-one (49805-30-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + (1R,4S)-4-aminocyclopenten-2-ene-1-carboxylic acid (134003-04-6)

Conditions	Yield
With Nocardia farcinica-polyamidase (NfpolyA) In aq. phosphate buffer at 30℃; for 24h; pH=7.5; Resolution of racemate; Enzymatic reaction;	A n/a B n/a C n/a

2-azabicyclo[2.2.1.]hept-5-en-3-one (49805-30-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + (1R,4S)-4-aminocyclopenten-2-ene-1-carboxylic acid (134003-04-6) + (-)-(1S, 4R)-4-amino-2-cyclopentene-1-carboxylic acid (102579-71-5, 102579-72-6, 102679-78-7, 134003-04-6, 134234-04-1)

Conditions	Yield
With Rhodococcus globerulus-amidase (AMI) In aq. phosphate buffer at 30℃; for 24h; pH=7.5; Resolution of racemate; Enzymatic reaction;	A n/a B n/a C n/a

racemic 2-azabicyclo[2.2.1]hept-5-en-3-one (49805-30-3) → (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + (-)-(1S, 4R)-4-amino-2-cyclopentene-1-carboxylic acid (102579-71-5, 102579-72-6, 102679-78-7, 134003-04-6, 134234-04-1)

Conditions	Yield
With water; lipase B from Candida antarctica In isopropyl alcohol at 60℃; for 0.5h; Enzymatic reaction;	A n/a B n/a C n/a

di-tert-butyl dicarbonate (24424-99-5) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → tert-butyl (1R,4S)-(-)-3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate (151792-53-9)

Conditions	Yield
With dmap; triethylamine In tetrahydrofuran	100%
With dmap In tetrahydrofuran at 20℃; for 3h;	99%
With dmap In dichloromethane for 16h; Inert atmosphere;	98%

methanol (67-56-1) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (–)-methyl (1S,4R)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride (229613-83-6)

Conditions	Yield
With thionyl chloride at 0℃; for 2h;	100%
With thionyl chloride at 0 - 20℃; for 14h;	100%
With thionyl chloride at 0℃;	100%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (+)-2-Azabicyclo<2.2.1>heptan-3-one (134003-03-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol at 20℃; for 5h; atmospheric pressure;	100%
With hydrogen; acetic acid; palladium on activated charcoal In ethyl acetate at 20℃; under 2068.59 Torr; for 1.5h;	98%
With palladium 10% on activated carbon; hydrogen In methanol for 3h;	98%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (1S,3R)-3-aminocyclopentanecarboxylic acid (71830-07-4)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In ethyl acetate at 20℃; for 24h;	100%
With hydrogen; palladium 10% on activated carbon In ethyl acetate at 20℃; for 24h;	100%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (1S,4R)-(-)ethyl-4-aminocyclopent-2-ene-1-carboxylate hydrochloride (229613-86-9)

Conditions	Yield
With hydrogenchloride In ethanol for 2h; Heating / reflux;	100%
With thionyl chloride In ethanol at 10 - 30℃; for 1h; Solvent; Reagent/catalyst;

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (1R,4S,5R,6S)-5,6-dihydroxy-2-azabicyclo[2.2.1]heptan-3-one (79200-55-8)

Conditions	Yield
With osmium(VIII) oxide; 4-methylmorpholine N-oxide In 1,4-dioxane at 0 - 20℃; for 3h;	98%
With osmium(VIII) oxide; 4-methylmorpholine N-oxide; 4-methylmorpholine 4-oxide monohydrate In 1,4-dioxane; water at 0 - 20℃; for 3h;	98%
With osmium(VIII) oxide; 4-methylmorpholine N-oxide In water; tert-butyl alcohol at 70℃; for 0.5h;	94%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + toluene-4-sulfonic acid (104-15-4) → (1S,cis)-4-amino-2-cyclopentene-1-carboxylic acid 4-toluenesulfonate

Conditions	Yield
In tetrahydrofuran; water at 20 - 60℃; for 18h; Ring cleavage;	97%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (-)-(1S,4R)-4-aminocyclopent-2-ene-1-carboxylic acid hydrochloride (130931-84-9)

Conditions	Yield
With hydrogenchloride	95%
With hydrogenchloride for 1h; Heating;
With hydrogenchloride; water at 80℃; for 2h;

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + acryloyl chloride (814-68-6) → C9H9NO2

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; Inert atmosphere;	95%

pent-4-enoyl chloride (39716-58-0) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → C11H13NO2

Conditions	Yield
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: pent-4-enoyl chloride In tetrahydrofuran at 20℃; Inert atmosphere;	91%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + benzoyl chloride (98-88-4) → (1R,4S)-2-Benzoyl-2-aza-bicyclo[2.2.1]hept-5-en-3-one

Conditions	Yield
In pyridine	90%

di-tert-butyl dicarbonate (24424-99-5) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → tert-butyl (1R,4S)-(+)-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate (702666-73-7)

Conditions	Yield
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether for 7h; Heating; Stage #2: di-tert-butyl dicarbonate at 25℃; for 14h; Further stages.;	87%
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether for 7h; Heating; Stage #2: di-tert-butyl dicarbonate at 20℃; for 14h; Further stages.;	52%

methanol (67-56-1) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (1R,3S)-methyl 3-aminocyclopentanecarboxylate hydrochloride

Conditions	Yield
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With palladium 10% on activated carbon; hydrogen In ethyl acetate at 20℃; for 12h; Stage #2: methanol With thionyl chloride at 0 - 20℃; for 24h;	84%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + p-methoxybenzyl chloride (824-94-2) → (1R,4S)-2-(p-Methoxybenzyl)-2-azabicyclo<2.2.1>-5-hepten-3-one (168960-17-6)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2h;	83%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 50℃; for 3h; Inert atmosphere;	75%
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: p-methoxybenzyl chloride With tetra-(n-butyl)ammonium iodide In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃; for 3h;	65%
With potassium hydroxide Yield given;
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With tetra-(n-butyl)ammonium iodide; sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: p-methoxybenzyl chloride In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 25℃; for 1h; Solvent; Reagent/catalyst; Temperature;

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + 4-iodo-2-methoxybenzoic acid-methyl ester (148490-97-5) → methyl 2-methoxy-4-((1R,4S)-3-oxo-2-azabicyclo[2.2.1]hept-5-en-2-yl)benzoate (1311258-54-4)

Conditions	Yield
With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine In toluene at 110℃; for 18h; Inert atmosphere;	74%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + 4-Methoxybenzyl alcohol (105-13-5) → (1R,4S)-2-(p-Methoxybenzyl)-2-azabicyclo<2.2.1>-5-hepten-3-one (168960-17-6)

Conditions	Yield
Stage #1: 4-Methoxybenzyl alcohol With hydrogenchloride In water for 1h; Stage #2: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 6.5h; Inert atmosphere;	73%

ethene (74-85-1) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (3S,5R)-(-)-3,5-divinylpyrrolidin-2-one

Conditions	Yield
tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In dichloromethane at 20℃; under 760.051 Torr; for 2.5h;	70%

oxirane (75-21-8) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (1R,4S)-2-(2-hydroxyethyl)-2-azabicyclo[2.2.1]hept-5-en-3-one

Conditions	Yield
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium diisopropyl amide In tetrahydrofuran for 1h; Stage #2: oxirane In tetrahydrofuran	67%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + benzyl chloroformate (501-53-1) → (1R,45)-benzyl 2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate

Conditions	Yield
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 60℃; for 27h; Inert atmosphere; Stage #2: benzyl chloroformate With trimethylamine In tetrahydrofuran; water at 0 - 20℃; for 48h;	63%

but-3-enoyl chloride (1470-91-3) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → C10H11NO2

Conditions	Yield
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: but-3-enoyl chloride In tetrahydrofuran at 20℃; Inert atmosphere;	63%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + benzenesulfonyl chloride (98-09-9) → (1R)-2-aza-2-(benzenesulfonyl)bicyclo[2.2.1]hept-5-ene-3-one

Conditions	Yield
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: benzenesulfonyl chloride In tetrahydrofuran; mineral oil at 20℃; for 1.5h; Inert atmosphere;	62%

diazomethane (186581-53-3, 908094-01-9) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (-)-exo-7-azatricyclo[3.2.1.02.4]octan-6-one

Conditions	Yield
palladium diacetate In diethyl ether at 20℃; for 24h;	62%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) + isoprene (78-79-5) → 2-(3-methylbut-2-enyl)-2-azabicyclo[2.2.1]hept-5-en-3-one

Conditions	Yield
With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; 1,3-bis-(diphenylphosphino)propane; sodium carbonate In toluene at 140℃; for 20h; Inert atmosphere; regioselective reaction;	55%

2-(chloromethyl)iodobenzene (59473-45-9) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → N-(2'-iodobenzyl)-2-aza-3-oxobicyclo[2.2.1]hept-5-ene (195830-50-3)

Conditions	Yield
Stage #1: (-)-2-azabicyclo[2.2.1]hept-5-en-3-one With sodium hydride In tetrahydrofuran at 20℃; for 1h; Metallation; Stage #2: 2-(chloromethyl)iodobenzene In tetrahydrofuran for 12h; Alkylation; Heating;	53%
With sodium hydride In tetrahydrofuran at 65℃; for 16h; Substitution;	53%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (1S,2R,4S,5R)-3-oxa-6-azatricyclo[3.2.1.02,4]octan-7-one (329910-40-9)

Conditions	Yield
With disodium hydrogenphosphate; sodium dihydrogenphosphate In water at 0℃; for 7h; pH=6;	26.16%

(-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → exo-cis-5,6-Dihydroxy-2-azabicyclo<2.2.1>heptan-3-one (77745-22-3)

Conditions	Yield
With potassium permanganate In acetone Inert atmosphere;	25%

acetic anhydride (108-24-7) + (-)-2-azabicyclo[2.2.1]hept-5-en-3-one (79200-56-9) → (-)-(1S,4R)-4-acetamidocyclopent-2-enylmethanol (130931-86-1)

Conditions	Yield
Yield given. Multistep reaction;

Upstream product

• 49805-30-3 racemic 2-azabicyclo[2.2.1]hept-5-en-3-one 
• 229613-83-6 (–)-methyl (1S,4R)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride 
• 49805-30-3 2-azabicyclo[2.2.1.]hept-5-en-3-one 
• 168773-38-4 (5S,6R)-5-<(tert-Butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone 
• 168773-36-2 (5S,6R)-5-Hydroxy-6-<(benzyloxy)methyl>-2-piperidinone 
• 168773-43-1 (5S,6R)-1-(p-Methoxybenzyl)-5-<(tert-butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone 
• 168773-58-8 Trifluoro-methanesulfonic acid (1R,4S)-2-(4-methoxy-benzyl)-3-oxo-2-aza-bicyclo[2.2.1]hept-5-en-6-yl ester 
• 168773-40-8 (5S,6R)-1-Benzyl-5-<(tert-butyldimethylsilyl)oxy>-6-<(benzyloxy)methyl>-2-piperidinone 
• 168773-46-4 (5S,6R)-1-(p-Methoxybenzyl)-5-<(tert-butyldimethylsilyl)oxy>-6-(bromomethyl)-2-piperidinone 
• 168773-44-2 (5S,6R)-1-(p-Methoxybenzyl)-5-<(tert-butyldimethylsilyl)oxy>-6-(hydroxymethyl)-2-piperidinone 
• 168773-47-5 (1R,4S,6S)-6-(tert-Butyldimethylsiloxy)-2-(p-methoxybenzyl)-2-azabicyclo<2.2.1>-3-heptanone 
• 168773-41-9 (5S,6R)-1-Benzyl-5-<(tert-butyldimethylsilyl)oxy>-6-(hydroxymethyl)-2-piperidinone 
• 168773-45-3 (5S,6R)-1-Benzyl-5-<(tert-butyldimethylsilyl)oxy>-6-(bromomethyl)-2-piperidinone 
• 168773-42-0 (1R,4S,6S)-6-(tert-Butyldimethylsiloxy)-2-benzyl-2-azabicyclo<2.2.1>-3-heptanone 

Downstream Products

• 229613-83-6 (–)-methyl (1S,4R)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride 
• 244075-39-6 (1S,2S,4R,5R)-3-Oxa-6-aza-tricyclo[3.2.1.0^2,4]octan-7-one 
• 329910-40-9 (1S,2R,4S,5R)-3-oxa-6-azatricyclo[3.2.1.02,4]octan-7-one 
• 134003-03-5 (+)-2-Azabicyclo<2.2.1>heptan-3-one 
• 918452-15-0 C₁₆H₁₉NO₄ 
• 918452-16-1 (1S,4R,6S)-6-hydroxy-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]-heptan-3-one 
• 169104-33-0 (1S,4R)-2-[(4-methoxyphenyl)methyl]-2-azabicyclo[2.2.1]hept-5-en-3-one 
• 640897-02-5 (1S,4S)-6-difluoromethylenyl-2-(4‘-methoxybenzyl)-2-azabicyclo[2.2.1]heptan-3-one 
• 452324-46-8 (-)-exo-7-azatricyclo[3.2.1.0^2.4]octan-6-one 
• 452324-48-0 (-)-cis-exo-2-amino-4-hydroxymethyl-bicyclo[3.1.0]hexane 
• 220507-10-8 1R-(-)-exo-cis-5,6-dimethylmethylenedioxy-2-azabicyclo[2.2.1]heptan-3-one 

Relevant articles and documents

Chemical preparation method of 2-azabicyclo [2.2.1] hept-5-ene-3-one with optical activity

The invention discloses a chemical preparation method of 2-azabicyclo [2.2.1] hept-5-ene-3-one with optical activity. The chemical preparation method comprises the following steps: racemic 2-azabicyclo [2.2.1] hept-5-ene-3-one which is easily available on the market is used as a raw material and is subjected to chemical resolution to obtain (+/-) 4-aminocyclopent-2-ene-1-carboxylic acid methyl ester with optical activity, (+/-) 4-aminocyclopent-2-ene-1-carboxylic acid is prepared by hydrolysis, and the (+/-) 4-aminocyclopent-2-ene-1-carboxylic acid is subjected to intramolecular condensation to obtain the 2-azabicyclo [2.2.1] hept-5-ene-3-one with optical activity. The method has the advantages that the use of an enzyme fermentation method is avoided, the repeatability is good, and the yield is high.

Enhanced enzymatic synthesis of the enantiopure intermediate for the blockbuster drug intermediate abacavir through a two-step enzymatic cascade reaction

A very efficient enzymatic two-step cascade reaction was devised (E?>?200) for the resolution of activated γ-lactams (±)-1 and (±)-2. The N-hydroxymethyl group worked as a traceless activating group, when the reactions were performed with H2O (0.5?equiv) in the presence of benzylamine (1?equiv) in i-Pr2O at 60?°C. The ring-opened enantiomerically pure γ-amino acids (1S,4R)-6 (ee?=?99%, intermediate of abacavir) and (1S,3R)-8 (ee?=?99%) and unreacted lactams (1S,4R)-1 and (1R,4S)-2 (ee???96%) were obtained in good yields (?43%). Treatment of (1S,4R)-1 and (1R,4S)-2 with 18% HCl or NH4OH resulted in (1R,4S)-6·HCl and (1S,3R)-8·HCl or (1S,4R)-3 and (1R,4S)-4 quantitatively, with ee???96%.

Green access to chiral Vince lactam in a buffer-free aqueous system using a newly identified substrate-tolerant (-)-γ-lactamase

A novel non-heme chloroperoxidase (SvGL) with promiscuous (-)-γ-lactamase activity towards Vince lactam was identified from Streptomyces viridochromogenes by genome data-mining. SvGL possesses high activity and excellent thermal stability and enantioselectivity. Furthermore, it is able to tolerate extremely high substrate concentrations (4.0 M, 436.5 g L-1). Using the newly discovered (-)-γ-lactamase as a biocatalyst, an efficient and environmentally benign process for the production of (+)-γ-lactam was developed. The process allowed an enantioselective resolution of 436.5 g L-1 racemic γ-lactam with only 0.2 g L-1 lyophilized cell-free extract, affording an extremely high substrate/catalyst ratio of 2183 (g g-1), a space-time yield of 458 g L-1 d-1, and a very low E factor (environmental factor) of 5.7 (kg waste per kg product) even when the process water is included.