130931-83-8

Basic information

• Product Name: (1S,4R)-2-Aza-bicyclo[2.2.1]hept-5-en-3-one
• Synonyms: (+)-VINCE'S LACTAM;(1S,4R)-2-AZA-BICYCLO[2.2.1]HEPT-5-EN-3-ONE;(1S)-(+)-2-AZABICYCLO[2.2.1]HEPT-5-EN-3-ONE;(1S)-(+)-2-AZABICYCLO(2.2.1)HEPT-5-EN-3- ONE, 98+% (99% EE/HPLC);(+)-2-AZABICYCLO[2.2.1]HEPT-5-EN-3-ONE 98% 95+% E.E.;(1R,4S)-3-Azabicyclo[2.2.1]hept-5-en-2-one;2-Azabicyclo[2.2.1]hept-5-en-3-one,(1S,4R)-;(1S)-(+)-2-Azabicyclo[2.2.1]hept-5-en-3-one >=98%
• CAS NO: 130931-83-8
• Molecular Formula: C₆H₇NO
• Molecular Weight: 109.13
• EINECS: 421-830-3
• Product Categories: Chiral Building Blocks;Lactams;Organic Building Blocks;API;Heterocycle-other series
• Mol File: 130931-83-8.mol
• Article Data: 23

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 crystalline powder
• Density: 1.199 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.546
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 15.48±0.20(Predicted)
• CAS DataBase Reference: (1S,4R)-2-Aza-bicyclo[2.2.1]hept-5-en-3-one(CAS DataBase Reference)
• NIST Chemistry Reference: (1S,4R)-2-Aza-bicyclo[2.2.1]hept-5-en-3-one(130931-83-8)
• EPA Substance Registry System: (1S,4R)-2-Aza-bicyclo[2.2.1]hept-5-en-3-one(130931-83-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 130931-83-8(Hazardous Substances Data)

Usage

Chemical Properties

OFF-WHITE TO BEIGE CRYSTALLINE POWDER

Uses

This lactam and its antipode are precursors to the enantiomers of the carbocyclic nucleoside carbovir. It has been demonstrated that (-)-carbovir is a potent inhibitor of HIV-1 and based on clinical trials it could become an alternative to AZT. AZT is a trademark of The Wellcome Foundation Ltd.

InChI:InChI=1/C6H7NO/c8-6-4-1-2-5(3-4)7-6/h1-2,4-5H,3H2,(H,7,8)/t4-,5+/m0/s1

Synthetic route

(1S,4R)-N-hydroxymethyl-2-azabicyclo<2.2.1>hept-5-en-3-one (157810-20-3) → (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
With ammonium hydroxide In methanol at 20℃; for 4h;	95%
With ammonium hydroxide In methanol for 12h; Ambient temperature;	45%
With methanol; ammonium hydroxide for 13h; Ambient temperature;	38%

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

Conditions	Yield
With resin-supported recombinant Candida antarctica lipase B; water In tert-butyl methyl ether at 60℃; for 102h; enantioselective reaction;	48%
With citrophilla (ATCC No.21285) In phosphate buffer for 24h; pH=7.5;	31.8%
With lipase B Candida antarctica recombined fromAspergillus oryzae In aq. phosphate buffer for 168h; Reagent/catalyst; Enzymatic reaction;	n/a
Multi-step reaction with 3 steps 1: Sonication 2: water; lipase B from Candida antarctica; benzylamine / isopropyl alcohol / 0.5 h / 60 °C / Enzymatic reaction 3: ammonium hydroxide / methanol / 4 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: Sonication 2: water; lipase B from Candida antarctica; benzylamine / isopropyl alcohol / 2 h / 60 °C / Enzymatic reaction 3: ammonium hydroxide / methanol / 4 h / 20 °C View Scheme

racemic 2-azabicyclo[2.2.1]hept-5-en-3-one (49805-30-3) → (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 lipase B from Candida antarctica In water; isopropyl alcohol at 60℃; for 4h; Enzymatic reaction; stereospecific reaction;	A 46% B 48%
With water In tert-butyl methyl ether Enzymatic reaction; optical yield given as %ee;

(1S,4R)-2-[(4-methoxyphenyl)methyl]-2-azabicyclo[2.2.1]hept-5-en-3-one (169104-33-0) → (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
With ammonium cerium(IV) nitrate In water; acetonitrile at 0℃; for 2.5h;	26%

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

(1R,6S)-6-Chlorocarbonyl-cyclohex-3-enecarboxylic acid isopropyl ester → (3aS,7aR)-3a,4,7,7a-tetrahydroisobenzofuran-1(3H)-one (88586-06-5) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
With sodium tetrahydroborate; camphor-10-sulfonic acid 1.) THF, EtOH, -40 degC, 3 h; 2.) toluene, reflux, 5 h; Yield given. Multistep reaction;

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-hydroxymethyl-2-azabicyclo<2.2.1>hept-5-en-3-one (157732-10-0) → (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
Multi-step reaction with 2 steps 2: 45 percent / aq. NH3 / methanol / 12 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 2: 38 percent / Nh4OH, MeOH / 13 h / Ambient temperature View Scheme

(1S,6R)-6-(isopropoxycarbonyl)cyclohex-3-enecarboxylic acid (181136-52-7) → (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: CH2Cl2 / 3 h / Ambient temperature 2: 1.) NaBH4; 2.) camphorsulfonic acid / 1.) THF, EtOH, -40 degC, 3 h; 2.) toluene, reflux, 5 h View Scheme

cis-1,2,3,6-tetrahydrophthalic anhydride (935-79-5) → (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) TADDOL / 1.) Et2O, r.t., 3 h; 2.) THF, -20 degC, 10 d 2: CH2Cl2 / 3 h / Ambient temperature 3: 1.) NaBH4; 2.) camphorsulfonic acid / 1.) THF, EtOH, -40 degC, 3 h; 2.) toluene, reflux, 5 h View Scheme

2-azabicyclo[2.2.1.]hept-5-en-3-one (49805-30-3) → (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 In tert-butyl methyl ether Enzymatic reaction; optical yield given as %ee; enantioselective reaction;
With Bradyrhizobium japonicum USDA 6 (−)-γ-lactamase In aq. buffer at 50℃; pH=6; Kinetics; Temperature; pH-value; Concentration; Enzymatic reaction; enantioselective reaction;	A n/a B n/a
With cyclic imide hydrolase(CIH) In aq. phosphate buffer at 30℃; for 24h; pH=7.5; Resolution of racemate; Enzymatic reaction;	A n/a B 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) + (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) → (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) + (-)-(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 non-heme chloroperoxidase (CPO-T) 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 N-hydroxymethyl vince lactam → (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: water; lipase B from Candida antarctica; benzylamine / isopropyl alcohol / 0.5 h / 60 °C / Enzymatic reaction 2: ammonium hydroxide / methanol / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: water; lipase B from Candida antarctica; benzylamine / isopropyl alcohol / 2 h / 60 °C / Enzymatic reaction 2: ammonium hydroxide / methanol / 4 h / 20 °C View Scheme

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

2-azabicyclo[2.2.1.]hept-5-en-3-one (49805-30-3) → C6H9NO2 + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
With chloroperoxidase In aq. phosphate buffer at 30℃; for 0.5h; pH=7; Kinetics; Reagent/catalyst; Temperature; Solvent; pH-value; Resolution of racemate; Green chemistry; Enzymatic reaction; enantioselective reaction;	A n/a B 2.1 g

2-azabicyclo[2.2.1.]hept-5-en-3-one (49805-30-3) → C6H9NO2 + (-)-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 CfGL2 In aq. phosphate buffer at 30℃; for 9h; pH=7; Resolution of racemate; Green chemistry; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a

(1S,4R)-4-aminocyclopent-2-ene-1-carboxylic acid methyl ester tartrate → (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; methanol; lithium hydroxide; water / -20 °C / pH 6 - 7 2: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate / N,N-dimethyl-formamide / 18 h / 45 °C View Scheme

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

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate In N,N-dimethyl-formamide at 45℃; for 18h;	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) + cis-4-amino-cyclopent-2-ene-1-carboxylic acid (102579-71-5, 102579-72-6, 102679-78-7, 134003-04-6, 134234-04-1)

Conditions	Yield
With (+) γ-lactamase immobilized on epoxy graphene oxide carrier In aq. phosphate buffer at 80℃; pH=8; Kinetics; Reagent/catalyst; Enzymatic reaction;

3-((2S,5R)-2-Isopropyl-5-methyl-cyclohexanesulfonyl)-2-aza-bicyclo[2.2.1]hepta-2,5-diene → (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8)

Conditions	Yield
With sodium hydroxide In water; acetic acid

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (-)-2-Azabicyclo<2.2.1>heptan-3-one (134003-02-4)

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%
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 2h;	98%

di-tert-butyl dicarbonate (24424-99-5) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (-)-[(1R,4S)-tert-butyl 3-oxo-2-azabicyclo(2.2.1)hept-5-ene-2-carboxylate] (200002-41-1)

Conditions	Yield
With dmap; triethylamine In tetrahydrofuran	100%
With pyridine; dmap at 20℃; for 3h;	100%
With dmap; triethylamine In tetrahydrofuran at 0 - 20℃;	93%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (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%
Multi-step reaction with 3 steps 1: 79 percent / bromine / CH2Cl2 / 0.25 h / Ambient temperature 2: 87 percent / tributyltin hydride, azobisisobutyronitrile / toluene / 5 h / Heating 3: 97 percent / aq. HCl / Heating View Scheme

methanol (67-56-1) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1R,4S)-methyl 4-aminocyclopent-2-enecarboxylate hydrochloride salt

Conditions	Yield
With thionyl chloride at 0 - 20℃; for 12h;	100%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (+)-methyl (1R,4S)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride

Conditions	Yield
With thionyl chloride; 2-azabicyclo[2.2.1.]hept-5-en-3-one In methanol at 20℃; for 2h;	100%
With thionyl chloride In methanol at 20℃; for 2h;	5.36 g

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → 2-Azabicyclo[2.2.1]heptan-3-one (24647-29-8)

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

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (+/-)-cis-4-amino-2-cyclopentene-1-carboxylic acid methanesulfonate

Conditions	Yield
	98.2%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1R,4R,6S,7R)-6,7-dibromo-2-azabicyclo[2.2.1]heptan-3-one (262280-21-7)

Conditions	Yield
With bromine In dichloromethane at 0℃; for 2h; Bromination;	98%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → C7H13NO2 (625108-11-4)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In ethyl acetate at 20℃; for 24h;	96%
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With hydrogen; palladium 10% on activated carbon In ethyl acetate at 20℃; for 24h; Stage #2: With hydrogenchloride In methanol; water at 20℃; for 72h;	96%
Multi-step reaction with 2 steps 1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 24 h / 20 °C 2: hydrogenchloride; water / 72 h / 20 °C View Scheme

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1S,3R)-3-amino-cyclopentanecarboxylic acid methyl ester hydrochloride

Conditions	Yield
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With hydrogen; palladium 10% on activated carbon In ethyl acetate for 24h; Stage #2: With hydrogenchloride In methanol; water at 20℃; for 72h;	96%
Multi-step reaction with 2 steps 1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 24 h / 20 °C 2: hydrogenchloride / water / 72 h / 20 °C View Scheme

methanol (67-56-1) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (+)-methyl (1R,4S)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride

Conditions	Yield
With thionyl chloride at 2 - 8℃; for 1.5h; Inert atmosphere; Industrial scale;	95%
With thionyl chloride at 0℃; for 2h;
With thionyl chloride at 0 - 13℃; for 4.25h;
With hydrogenchloride In water for 16h; Sealed tube; Heating;

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + 1-Bromo-2-butyne (3355-28-0) → (1S,4R)-2-But-2-ynyl-2-aza-bicyclo[2.2.1]hept-5-en-3-one (666256-77-5)

Conditions	Yield
With potassium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate	92%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + allyl bromide (106-95-6) → (1S)-2-(allyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (406218-20-0)

Conditions	Yield
With potassium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile for 3h; Heating;	90%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (+)-(1R,4S)-4-aminocyclopent-2-ene-1-carboxylic acid hydrochloride (130931-85-0)

Conditions	Yield
With hydrogenchloride In water for 2h; Reflux;	90%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + methyl iodide (74-88-4) → (1S,4R)-2-methyl-2-azabicyclo[2.2.1]hept-5-en-3-one

Conditions	Yield
With caesium carbonate In butanone at 35℃; Inert atmosphere;	90%
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 0.5h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 20℃; for 16h;	75%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + p-methoxybenzyl chloride (824-94-2) → (1S,4R)-2-[(4-methoxyphenyl)methyl]-2-azabicyclo[2.2.1]hept-5-en-3-one (169104-33-0)

Conditions	Yield
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: p-methoxybenzyl chloride With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃;	90%
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.0833333h; Stage #2: p-methoxybenzyl chloride With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 4.5h;	21.4 g

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + p-methoxybenzyl chloride (824-94-2) → (1S,4R)-2-[(4-methoxyphenyl)methyl]-2-azabicyclo[2.2.1]hept-5-en-3-one

Conditions	Yield
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: p-methoxybenzyl chloride With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide; mineral oil at 0℃;	90%

ethanol (64-17-5) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1R,4S)-ethyl 4-aminocyclopent-2-enecarboxylate hydrochloride (229613-87-0)

Conditions	Yield
With hydrogenchloride at 0℃; for 1h;	89%
With hydrogenchloride In water at 0℃; for 1h;	73%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + 4-methoxycarbonylphenylboronic acid (99768-12-4) → methyl 4-((1S,4S,6R)-3-oxo-2-azabicyclo[2.2.1]heptan-6-yl)benzoate

Conditions	Yield
With [Rh(OH)(cod)]2; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene In tetrahydrofuran; water at 23℃; for 64h; Inert atmosphere; regioselective reaction;	89%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (+)-cis-4-amino-2-cyclopentene-1-methanol

Conditions	Yield
	88.8%

tert-butyldicarbonate (34619-03-9) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1R,4S)-N-(tert-Butyloxycarbonyl)-1-amino-4-(hydroxymethyl)-2-cyclopentene (168960-18-7)

Conditions	Yield
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With methanesulfonic acid In tetrahydrofuran; water at 34 - 44℃; for 2.75h; Heating / reflux; Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran for 18.5h; Heating / reflux; Stage #3: tert-butyldicarbonate With sodium fluoride more than 3 stages;	88%

2-Methylphenylboronic acid (16419-60-6) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1S,4S,6R)-6-(o-tolyl)-2-azabicyclo[2.2.1]heptan-3-one

Conditions	Yield
With [Rh(OH)(cod)]2; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene In tetrahydrofuran; water at 23℃; for 64h; Inert atmosphere; regioselective reaction;	87%

benzyl bromide (100-39-0) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1S,4R)-2-benzyl-2-azabicyclo[2.2.1 ]hept-5-en-3-one

Conditions	Yield
Stage #1: (1S,4R)-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 1h; Inert atmosphere; Stage #2: benzyl bromide In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 20℃; Inert atmosphere;	87%
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: benzyl bromide at 20℃; for 72h;

di-tert-butyl dicarbonate (24424-99-5) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1R,4S)-tert-butyl 3-oxo-2-azabicyclo[2.2.1]heptane-2-carboxylate (204913-00-8)

Conditions	Yield
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With hydrogen; palladium 10% on activated carbon In methanol under 2585.81 Torr; for 1h; Stage #2: di-tert-butyl dicarbonate With dmap In dichloromethane at 20℃;	86%
Stage #1: (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one With palladium 10% on activated carbon; hydrogen In methanol at 40℃; under 7500.75 Torr; Stage #2: di-tert-butyl dicarbonate With dmap In acetonitrile at 20℃; for 2h;	1.94 g

3-methoxyphenylboronic acid (10365-98-7) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1S,4S,6R)-6-(3-methoxyphenyl)-2-azabicyclo[2.2.1]heptan-3-one

Conditions	Yield
With [Rh(OH)(cod)]2; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene In tetrahydrofuran; water at 23℃; for 64h; Inert atmosphere; regioselective reaction;	86%

1-bromo-4-butene (5162-44-7) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1S)-2-(but-3-enyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (406218-21-1)

Conditions	Yield
With potassium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile for 3h; Heating;	85%

(1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) + propargyl bromide (106-96-7) → (1S,4R)-2-Prop-2-ynyl-2-aza-bicyclo[2.2.1]hept-5-en-3-one (666256-76-4)

Conditions	Yield
With potassium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate	85%

4-trifluoromethylphenylboronic acid (128796-39-4) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1S,4S,6R)-6-(4-(trifluoromethyl)phenyl)-2-azabicyclo[2.2.1]heptan-3-one

Conditions	Yield
With [Rh(OH)(cod)]2; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene In tetrahydrofuran; water at 23℃; for 17h; Inert atmosphere; regioselective reaction;	83%

4-Bromophenylboronic acid (5467-74-3) + (1S,4R)-2-azabicyclo[2,2,1]hept-5-en-3-one (130931-83-8) → (1S,4S,6R)-6-(4-bromophenyl)-2-azabicyclo[2.2.1]heptan-3-one

Conditions	Yield
With [Rh(OH)(cod)]2; (2S)-1-[(1S)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene In tetrahydrofuran; water at 23℃; for 64h; Inert atmosphere; regioselective reaction;	83%

Upstream product

• 49805-30-3 racemic 2-azabicyclo[2.2.1]hept-5-en-3-one 
• 102579-71-5 (-)-(1S, 4R)-4-amino-2-cyclopentene-1-carboxylic acid 
• 419563-22-7 (1S,4R)-4-aminocyclopent-2-ene-1-carboxylic acid methyl ester tartrate 
• 49805-30-3 2-azabicyclo[2.2.1.]hept-5-en-3-one 
• 935-79-5 cis-1,2,3,6-tetrahydrophthalic anhydride 
• 181136-52-7 (1S,6R)-6-(isopropoxycarbonyl)cyclohex-3-enecarboxylic acid 
• 157732-10-0 2-hydroxymethyl-2-azabicyclo<2.2.1>hept-5-en-3-one 
• 169104-33-0 (1S,4R)-2-[(4-methoxyphenyl)methyl]-2-azabicyclo[2.2.1]hept-5-en-3-one 
• 157810-20-3 (1S,4R)-N-hydroxymethyl-2-azabicyclo<2.2.1>hept-5-en-3-one 

Downstream Products

• 666256-77-5 (1S,4R)-2-But-2-ynyl-2-aza-bicyclo[2.2.1]hept-5-en-3-one 
• 666256-76-4 (1S,4R)-2-Prop-2-ynyl-2-aza-bicyclo[2.2.1]hept-5-en-3-one 
• 255372-19-1 N-((1S,4R)-4-Hydroxymethyl-cyclopent-2-enyl)-4-methyl-benzenesulfonamide 
• 204912-99-2 C₂₂H₂₅NO₆S₂ 
• 168960-18-7 (1R,4S)-N-(tert-Butyloxycarbonyl)-1-amino-4-(hydroxymethyl)-2-cyclopentene 
• 141271-11-6 (-)-(1S,4R)-4-<(2'-amino-6'-chloropyrimidin-4'-yl)amino>-cyclopent-2-enylmethanol 
• 130931-85-0 (+)-(1R,4S)-4-aminocyclopent-2-ene-1-carboxylic acid hydrochloride 

Relevant articles and documents

Optical resolution of 2-azabicyclo[2.2.1]hept-5-en-3-one by inclusion complexation with brucine

A simple optical resolution method of 2-azabicyclo[2.2.1]hept-5-en-3-one by inclusion complexation with brucine was reported. The crystal structure of the inclusion complex was analyzed by X-Ray diffraction in order to elucidate the mechanism of the efficient chiral recognition in the inclusion crystals.

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.

Synthesis of rigid bicycloheterocyclic scaffolds from Vince's lactam (enzymatic resolution of Vince's lactam)

Vince's lactam, on oxidative cleavage and reduction, produced the 3,5-dihydroxymethylpyrrolidin-2-one derivative. This precursor has been utilized in intramolecular cyclization reactions to design some unique diaza-, oxaaza-, and thiaaza-bicyclic molecules as potential scaffolds in combinatorial chemistry.

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%.