110567-22-1

Basic information

• Product Name: (1S,2R,3S,5R)-3-(Phenymethyloxy)-2-(phenylmethoxy)methyl-6-oxabicyclo[3.1.0]hexane
• Synonyms: (1S,2R,3S,5R)-3-(Phenymethyloxy)-2-(phenylmethoxy)methyl-6-oxabicyclo[3.1.0]hexane;(1S,2R,3S,5R)-3-(Phenylmethoxy)-2-[(phenylmethoxy)methyl]-6-oxabicyclo[3.1.0]hexane;[1S-(1a,2a,3,5a)]-3-(Phenylmethoxy)-2-[(phenylmethoxy)methyl]-6-oxabicyclo[3.1.0]hexane;6-Oxabicyclo[3.1.0]hexane, 3-(phenylmethoxy)-2-[(phenylmethoxy)methyl]-, (1S, 2R, 3S, 5R);(1S,2R,3S,5R)-3-(Benzyloxymethyl)-6-oxabicyclo[3.1.0]hexane;[1S-(1α,2α,3β,5α)]-3-(Phenylmethoxy)-2-[(phenylmethoxy)methyl]-6-oxabicyclo[3.1.0]hexane;(1S,2R,3S,5R)-3-(Phenylmethoxy)-2-[(phenylmethoxy)methyl]-6-oxabicyclo[3.1.0]hexane ,90%;1R,2R-2-[(Phenylmethoxy)methyl]-3-cyclo penten-1-ol
• CAS NO: 110567-22-1
• Molecular Formula: C₂₀H₂₂O₃
• Molecular Weight: 310.38688
• EINECS: 1592732-453-0
• Product Categories: Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 110567-22-1.mol

Chemical Properties

• Boiling Point: 427.928 °C at 760 mmHg
• Flash Point: 145.852 °C
• Appearance: /
• Density: 1.17
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.593
• Storage Temp.: Refrigerator
• Solubility: Benzene, Chloroform, DMSO, Methanol
• CAS DataBase Reference: (1S,2R,3S,5R)-3-(Phenymethyloxy)-2-(phenylmethoxy)methyl-6-oxabicyclo[3.1.0]hexane(CAS DataBase Reference)
• NIST Chemistry Reference: (1S,2R,3S,5R)-3-(Phenymethyloxy)-2-(phenylmethoxy)methyl-6-oxabicyclo[3.1.0]hexane(110567-22-1)
• EPA Substance Registry System: (1S,2R,3S,5R)-3-(Phenymethyloxy)-2-(phenylmethoxy)methyl-6-oxabicyclo[3.1.0]hexane(110567-22-1)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 110567-22-1(Hazardous Substances Data)

Usage

Chemical Properties

Colorless Oil

Uses

Different sources of media describe the Uses of 110567-22-1 differently. You can refer to the following data:
1. Entecavir intermediate.
2. Entecavir intermediate

InChI:InChI=1/C20H22O3/c1-3-7-15(8-4-1)12-21-14-17-18(11-19-20(17)23-19)22-13-16-9-5-2-6-10-16/h1-10,17-20H,11-14H2/t17-,18+,19-,20+/m1/s1

Synthetic route

benzyl bromide (100-39-0) + (2R,3S)-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexan-3-ol (117641-39-1) → (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1)

Conditions	Yield
Stage #1: (2R,3S)-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexan-3-ol With sodium hydride In tetrahydrofuran at 20℃; for 1h; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide In tetrahydrofuran at 20℃; for 12h;	86%
With tetra-(n-butyl)ammonium iodide; sodium hydride 1.) THF, 2 h; 1.) THF, 2.5 h; Yield given. Multistep reaction;
With tetra-(n-butyl)ammonium iodide; sodium hydride In N,N-dimethyl-formamide Yield given;
With tetra-(n-butyl)ammonium iodide; sodium hydride In N,N-dimethyl-formamide; mineral oil at -50℃; for 18h;
With sodium hydride In tetrahydrofuran; water at 20℃; Large scale;	4.4 kg

Benzyloxymethyl chloride (3587-60-8) → (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h / 0 °C 1.2: tetrahydrofuran / 2 h / -40 °C 2.1: (-)-diisopinocamphenylborane / tetrahydrofuran / 17 h / -60 - 0 °C 2.2: 8.20 g / aq. NaOH; H2O2 / diethyl ether; tetrahydrofuran / 12 h / 0 °C 3.1: 82 percent / Mo(CO)6; t-BuOOH / benzene; decane / 3 h / 80 °C 4.1: NaH / tetrahydrofuran / 1 h / 20 °C 4.2: 86 percent / tetrabutylammonium iodide / tetrahydrofuran / 12 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: tetrahydrofuran / -78 - -65 °C 2: 1.) diisopinylcampheylborane (prepared from (+)-α-pinene), 2.) aq. NaOH, H2O2 / 1.) THF, -65 to -78 deg C 3: VO(acac)2, t-BuOOH / CH2Cl2 4: NaH, Bu4NI / dimethylformamide View Scheme
Multi-step reaction with 4 steps 1: 1.) Na / 1.) THF, -5 deg C, 1.5 h; 2.) THF, -45 deg C, 1 h 2: 15.8 g / (-)-diisopinan-3-ylborane / tetrahydrofuran / 1.) -60 deg C, 1 h; 2.) 5 deg C, 18 h 3: 12.0 g / t-butyl hydroperoxide, vanadium(V)acetylacetonate / 1,2-dichloro-ethane / 2.75 h / 30 °C 4: 1.) NaH; 2.) tetrabutylammonium iodide / 1.) THF, 2 h; 1.) THF, 2.5 h View Scheme

5-(benzyloxymethyl)cyclopentadiene (39939-07-6) → (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: (-)-diisopinocamphenylborane / tetrahydrofuran / 17 h / -60 - 0 °C 1.2: 8.20 g / aq. NaOH; H2O2 / diethyl ether; tetrahydrofuran / 12 h / 0 °C 2.1: 82 percent / Mo(CO)6; t-BuOOH / benzene; decane / 3 h / 80 °C 3.1: NaH / tetrahydrofuran / 1 h / 20 °C 3.2: 86 percent / tetrabutylammonium iodide / tetrahydrofuran / 12 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 1.) diisopinylcampheylborane (prepared from (+)-α-pinene), 2.) aq. NaOH, H2O2 / 1.) THF, -65 to -78 deg C 2: VO(acac)2, t-BuOOH / CH2Cl2 3: NaH, Bu4NI / dimethylformamide View Scheme
Multi-step reaction with 3 steps 1: 15.8 g / (-)-diisopinan-3-ylborane / tetrahydrofuran / 1.) -60 deg C, 1 h; 2.) 5 deg C, 18 h 2: 12.0 g / t-butyl hydroperoxide, vanadium(V)acetylacetonate / 1,2-dichloro-ethane / 2.75 h / 30 °C 3: 1.) NaH; 2.) tetrabutylammonium iodide / 1.) THF, 2 h; 1.) THF, 2.5 h View Scheme

cyclopenta-1,3-diene (542-92-7) + (AsCF3)4.5 → (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran / 1 h / 0 °C 1.2: tetrahydrofuran / 2 h / -40 °C 2.1: (-)-diisopinocamphenylborane / tetrahydrofuran / 17 h / -60 - 0 °C 2.2: 8.20 g / aq. NaOH; H2O2 / diethyl ether; tetrahydrofuran / 12 h / 0 °C 3.1: 82 percent / Mo(CO)6; t-BuOOH / benzene; decane / 3 h / 80 °C 4.1: NaH / tetrahydrofuran / 1 h / 20 °C 4.2: 86 percent / tetrabutylammonium iodide / tetrahydrofuran / 12 h / 20 °C View Scheme

(1S,2R)-2-(benzyloxymethyl)-1-hydroxy-3-cyclopentene (110567-21-0) → (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 82 percent / Mo(CO)6; t-BuOOH / benzene; decane / 3 h / 80 °C 2.1: NaH / tetrahydrofuran / 1 h / 20 °C 2.2: 86 percent / tetrabutylammonium iodide / tetrahydrofuran / 12 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: VO(acac)2, t-BuOOH / CH2Cl2 2: NaH, Bu4NI / dimethylformamide View Scheme
Multi-step reaction with 2 steps 1: 12.0 g / t-butyl hydroperoxide, vanadium(V)acetylacetonate / 1,2-dichloro-ethane / 2.75 h / 30 °C 2: 1.) NaH; 2.) tetrabutylammonium iodide / 1.) THF, 2 h; 1.) THF, 2.5 h View Scheme
Multi-step reaction with 2 steps 1.1: tert.-butylhydroperoxide; bis(acetylacetonate)oxovanadium / dichloromethane / 16 h / 20 °C / Large scale 1.2: 1 h / 20 °C / Large scale 2.1: sodium hydride / water; tetrahydrofuran / 20 °C / Large scale View Scheme

sodium cyclopentadienylide (4984-82-1) → (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrahydrofuran / -78 - -65 °C 2: 1.) diisopinylcampheylborane (prepared from (+)-α-pinene), 2.) aq. NaOH, H2O2 / 1.) THF, -65 to -78 deg C 3: VO(acac)2, t-BuOOH / CH2Cl2 4: NaH, Bu4NI / dimethylformamide View Scheme

cyclopenta-1,3-diene (542-92-7) → (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) Na / 1.) THF, -5 deg C, 1.5 h; 2.) THF, -45 deg C, 1 h 2: 15.8 g / (-)-diisopinan-3-ylborane / tetrahydrofuran / 1.) -60 deg C, 1 h; 2.) 5 deg C, 18 h 3: 12.0 g / t-butyl hydroperoxide, vanadium(V)acetylacetonate / 1,2-dichloro-ethane / 2.75 h / 30 °C 4: 1.) NaH; 2.) tetrabutylammonium iodide / 1.) THF, 2 h; 1.) THF, 2.5 h View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (1S,2R,3S,5R)-2-Hydroxymethyl-6-oxa-bicyclo[3.1.0]hexan-3-ol (117641-42-6)

Conditions	Yield
With hydrogen; palladium on activated charcoal	100%

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (1S,2S,3S,5S)-5-azido-3-(benzyloxy)-2-(benzyloxymethyl)cyclopentanol (110567-23-2)

Conditions	Yield
With sodium azide; ammonium chloride In ethanol at 85℃; for 22h;	99%
With sodium azide; ammonium chloride In ethanol at 85℃; for 22h;

C17H19N5O3 (1351691-90-1) + (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → C37H41N5O6

Conditions	Yield
Stage #1: C17H19N5O3 With lithium hydride In N,N-dimethyl-formamide at 60℃; for 0.25h; Stage #2: (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane In N,N-dimethyl-formamide at 125℃; for 2.5h;	83%

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) + potassium cyanide (151-50-8) → (1S,2R,3R,4R)-1-Benzyloxy-2-benzyloxymethyl-4-cyano-3-hydroxycyclopentane (160860-62-8)

Conditions	Yield
With lithium perchlorate In acetonitrile at 70℃; for 96h;	77.5%
With lithium perchlorate In acetonitrile at 70℃; for 24h;	75%

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) + 2,4-dihydroxy-5-methylpyrimidine (65-71-4) → 1-(3',5'-di-O-benzyl-2'-deoxy-6'-hydroxy-6'-carba-β-D-ribofuranosyl)thymine (114071-49-7)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 140℃;	70%

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) + thymin (65-71-4) → 1-(3',5'-di-O-benzyl-2'-deoxy-6'-hydroxy-6'-carba-β-D-ribofuranosyl)thymine (114071-49-7)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 140℃;	70%
With lithium hydride In N,N-dimethyl-formamide at 140℃;	64%
Stage #1: thymin With triethylaluminum In tetrahydrofuran; hexane at 20℃; for 1h; Stage #2: (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane In tetrahydrofuran; hexane at 20℃; for 48h; ultrasound;	46%
In N-methyl-acetamide; methanol; dichloromethane; acetic acid; toluene; mineral oil

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) + adenine (66224-66-6, 66224-67-7, 66224-68-8, 66224-69-9, 134434-48-3, 134434-49-4, 134454-76-5, 134461-75-9) → [1S-(1α,2β,3α,5β)]-5-(6-amino-9H-purin-9-yl)-3-(phenylmethoxy)-2-[(phenylmethoxy)methyl]cyclopentanol (142217-96-7)

Conditions	Yield
With lithium hydride In N,N-dimethyl-formamide at 120℃;	70%

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) + uracil (66-22-8) → [1S-(1α,2β,3α,4β)]-1-[2-Hydroxy-4-(phenyl-methoxy)-3-[(phenylmethoxy)methyl]cyclopentyl]-2,4(1H,3H)-pyrimidinedione (114071-48-6)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 130℃;	65%
With sodium hydride In N,N-dimethyl-formamide at 140℃;	63%
With acetic acid In N-methyl-acetamide; methanol; dichloromethane; mineral oil

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) + 2-Amino-6-benzyloxypurine (19916-73-5) → [1S-(1α,2β,3α,5β)]-5-(2-amino-6-benzyloxy-9H-purin-9-yl)-3-benzyloxy-2-(benzyloxy)methyl-cyclopentanol (142217-77-4)

Conditions	Yield
With lithium hydride In N,N-dimethyl-formamide at 125℃; for 2h;	60%
Stage #1: 2-Amino-6-benzyloxypurine With lithium hydride In N,N-dimethyl-formamide at 20 - 60℃; for 0.416667h; Stage #2: (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane In N,N-dimethyl-formamide at 60 - 125℃; for 2.25h;	51.18%
With acetic acid In N-methyl-acetamide; methanol; ethanol; dichloromethane; chloroform
With tetrabutylammomium bromide; potassium hydroxide In toluene at 80℃; for 6h; Temperature; Reagent/catalyst;	6 g

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) + 2-[(triphenylmethyl)amino]-6-benzyloxy-9H-purine → (1S,2S,3S,5S)-3-(benzyloxy)-5-[6-(benzyloxy)-2-[(triphenylmethyl)amino]-9H-purin-9-yl]-2-[(benzyloxy)methyl]cyclopentan-1-ol

Conditions	Yield
Stage #1: 2-[(triphenylmethyl)amino]-6-benzyloxy-9H-purine With lithium hydride In N,N-dimethyl-formamide at 58 - 62℃; for 0.5h; Stage #2: (2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane In N,N-dimethyl-formamide at 60 - 120℃; for 0.5h;	58.5%

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) + 2-amino-6-methoxyethoxypurine → (1S,2S,3S,5S)-5-[2-Amino-6-(2-methoxy-ethoxy)-purin-9-yl]-3-benzyloxy-2-benzyloxymethyl-cyclopentanol (114071-50-0)

Conditions	Yield
lithium hydride In N,N-dimethyl-formamide at 145℃;

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (1S,2S,3S,5S)-5-azido-3-(benzyloxy)-2-(benzyloxymethyl)cyclopentanol (110567-23-2) + (1R,2R,3R,4S)-2-Azido-4-benzyloxy-3-benzyloxymethyl-cyclopentanol

Conditions	Yield
With sodium azide; ammonium chloride In ethanol; water for 22h; Heating;	A 3.3 g B 0.2 g

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → 5'-O-[1-(2'-deoxy-6'-carba-β-D-ribofuranosyl)thymidinyl]monophosphate

Conditions

Yield

Multi-step reaction with 7 steps 1.1: Et3Al / hexane; tetrahydrofuran / 1 h / 20 °C 1.2: 46 percent / hexane; tetrahydrofuran / 48 h / 20 °C / ultrasound 2.1: DMAP / acetonitrile / 16 h / 20 °C 3.1: 398 mg / AIBN; n-Bu3SnH / toluene / 3.5 h / 75 °C 4.1: 90 percent / BCl3 / CH2Cl2 / 5 h / -78 °C 5.1: i-Pr2NEt / acetonitrile; dimethylformamide / 2 h / -40 - 0 °C 6.1: 107 mg / t-BuOOH / acetonitrile; dimethylformamide / 2 h / -40 - 20 °C 7.1: 76 percent / Et3N; H2O / acetonitrile / 18 h / 20 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → 1-((1R,3S,4R)-3-hydroxy-4-(hydroxymethyl)cyclopentyl)-5-methylpyrimidine-2,4(1H,3H)-dione (114884-15-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: Et3Al / hexane; tetrahydrofuran / 1 h / 20 °C 1.2: 46 percent / hexane; tetrahydrofuran / 48 h / 20 °C / ultrasound 2.1: DMAP / acetonitrile / 16 h / 20 °C 3.1: 398 mg / AIBN; n-Bu3SnH / toluene / 3.5 h / 75 °C 4.1: 90 percent / BCl3 / CH2Cl2 / 5 h / -78 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → 1-(3',5'-di-O-benzyl-2'-deoxy-6'-carba-β-D-ribofuranosyl)thymine (648414-58-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: Et3Al / hexane; tetrahydrofuran / 1 h / 20 °C 1.2: 46 percent / hexane; tetrahydrofuran / 48 h / 20 °C / ultrasound 2.1: DMAP / acetonitrile / 16 h / 20 °C 3.1: 398 mg / AIBN; n-Bu3SnH / toluene / 3.5 h / 75 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → 1-{(3S,1R,4R)-3-hydroxy-4-(8-methyl-2-oxo(4H-benzo[d]1,3,2-dioxaphosphan-2-yloxy)methylcyclopentyl)}-5-methyl-1,3-dihydropyrimidine-2,4(1H,3H)-dione

Conditions	Yield
Multi-step reaction with 5 steps 1.1: Et3Al / hexane; tetrahydrofuran / 1 h / 20 °C 1.2: 46 percent / hexane; tetrahydrofuran / 48 h / 20 °C / ultrasound 2.1: DMAP / acetonitrile / 16 h / 20 °C 3.1: 398 mg / AIBN; n-Bu3SnH / toluene / 3.5 h / 75 °C 4.1: 90 percent / BCl3 / CH2Cl2 / 5 h / -78 °C 5.1: i-Pr2NEt / acetonitrile; dimethylformamide / 2 h / -40 - 0 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → 3-methyl-cyclosaligenyl-5'-O-[1-(2'-deoxy-6'-carba-β-D-ribofuranosyl)thymidinyl]-phosphate (648414-62-4)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: Et3Al / hexane; tetrahydrofuran / 1 h / 20 °C 1.2: 46 percent / hexane; tetrahydrofuran / 48 h / 20 °C / ultrasound 2.1: DMAP / acetonitrile / 16 h / 20 °C 3.1: 398 mg / AIBN; n-Bu3SnH / toluene / 3.5 h / 75 °C 4.1: 90 percent / BCl3 / CH2Cl2 / 5 h / -78 °C 5.1: i-Pr2NEt / acetonitrile; dimethylformamide / 2 h / -40 - 0 °C 6.1: 107 mg / t-BuOOH / acetonitrile; dimethylformamide / 2 h / -40 - 20 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → thiocarbonic acid O-[3-benzyloxy-2-benzyloxymethyl-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-cyclopentyl] ester O-phenyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1.1: Et3Al / hexane; tetrahydrofuran / 1 h / 20 °C 1.2: 46 percent / hexane; tetrahydrofuran / 48 h / 20 °C / ultrasound 2.1: DMAP / acetonitrile / 16 h / 20 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (S)-Methanocarba-Thymidine (156044-00-7)

Conditions

Yield

Multi-step reaction with 11 steps 1: 77.5 percent / LiClO4 / acetonitrile / 96 h / 70 °C 2: 98 percent / 1,1'-thiocarbonyldiimidazole, DMAP / dimethylformamide / 1.) r.t., 3 h, 2.) 70 deg C, 30 min 3: 96.5 percent / CHCl3; diethyl ether / 72 h / 0 °C 4: benzophenone / benzene; acetonitrile / 2 h / Irradiation 5: 25percent aq. NaOH / methanol / 24 h / Heating 6: Et3N, DPPA / toluene / 1.) r.t., 2 h, 2.) 80 deg C, 2 h 7: toluene / 1.) 80 deg C, 2 h, 2.) r.t., overnight 8: 99 percent / Bu4NF / acetonitrile; tetrahydrofuran / 4 h / 70 °C 9: 85.5 percent / CH2Cl2 / 24 h / Ambient temperature 10: 2 M HCl / ethanol / 30 h / Heating 11: 87.72 percent / HCOOH / Pd / methanol / 2 h / 40 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (1S,3S,4R,5S)-3-Benzyloxy-4-benzyloxymethyl-1-aminobicyclo<3.1.0>hexane (170453-02-8)

Conditions

Yield

Multi-step reaction with 8 steps 1: 77.5 percent / LiClO4 / acetonitrile / 96 h / 70 °C 2: 98 percent / 1,1'-thiocarbonyldiimidazole, DMAP / dimethylformamide / 1.) r.t., 3 h, 2.) 70 deg C, 30 min 3: 96.5 percent / CHCl3; diethyl ether / 72 h / 0 °C 4: benzophenone / benzene; acetonitrile / 2 h / Irradiation 5: 25percent aq. NaOH / methanol / 24 h / Heating 6: Et3N, DPPA / toluene / 1.) r.t., 2 h, 2.) 80 deg C, 2 h 7: toluene / 1.) 80 deg C, 2 h, 2.) r.t., overnight 8: 99 percent / Bu4NF / acetonitrile; tetrahydrofuran / 4 h / 70 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (3R,4S)-1-Cyano-4-benzyloxy-3-benzyloxymethylcyclopentene (170452-98-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77.5 percent / LiClO4 / acetonitrile / 96 h / 70 °C 2: 98 percent / 1,1'-thiocarbonyldiimidazole, DMAP / dimethylformamide / 1.) r.t., 3 h, 2.) 70 deg C, 30 min View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (1S,3S,4R,5S)-3-Benzyloxy-4-benzyloxymethyl-1-cyanobicyclo<3.1.0>hexane (170453-00-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 77.5 percent / LiClO4 / acetonitrile / 96 h / 70 °C 2: 98 percent / 1,1'-thiocarbonyldiimidazole, DMAP / dimethylformamide / 1.) r.t., 3 h, 2.) 70 deg C, 30 min 3: 96.5 percent / CHCl3; diethyl ether / 72 h / 0 °C 4: benzophenone / benzene; acetonitrile / 2 h / Irradiation View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (1S,3S,4R,5S)-3-Benzyloxy-4-benzyloxymethylbicyclo<3.1.0>hexane-1-carboxylic acid (190195-74-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 77.5 percent / LiClO4 / acetonitrile / 96 h / 70 °C 2: 98 percent / 1,1'-thiocarbonyldiimidazole, DMAP / dimethylformamide / 1.) r.t., 3 h, 2.) 70 deg C, 30 min 3: 96.5 percent / CHCl3; diethyl ether / 72 h / 0 °C 4: benzophenone / benzene; acetonitrile / 2 h / Irradiation 5: 25percent aq. NaOH / methanol / 24 h / Heating View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (3aR,4R,5S,6aR)-4-Benzyloxymethyl-5-benzyloxy-6a-cyano-3,3a,4,5,6,6a-hexahydrocyclopentapyrazole (170452-99-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 77.5 percent / LiClO4 / acetonitrile / 96 h / 70 °C 2: 98 percent / 1,1'-thiocarbonyldiimidazole, DMAP / dimethylformamide / 1.) r.t., 3 h, 2.) 70 deg C, 30 min 3: 96.5 percent / CHCl3; diethyl ether / 72 h / 0 °C View Scheme

(2R,3S)-benzyloxy-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexane (110567-22-1) → (1S,3S,4R,5S)-3-Benzyloxy-4-benzyloxymethyl-1-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)bicyclo<3.1.0>hexane (190195-79-0)

Conditions

Yield

Multi-step reaction with 10 steps 1: 77.5 percent / LiClO4 / acetonitrile / 96 h / 70 °C 2: 98 percent / 1,1'-thiocarbonyldiimidazole, DMAP / dimethylformamide / 1.) r.t., 3 h, 2.) 70 deg C, 30 min 3: 96.5 percent / CHCl3; diethyl ether / 72 h / 0 °C 4: benzophenone / benzene; acetonitrile / 2 h / Irradiation 5: 25percent aq. NaOH / methanol / 24 h / Heating 6: Et3N, DPPA / toluene / 1.) r.t., 2 h, 2.) 80 deg C, 2 h 7: toluene / 1.) 80 deg C, 2 h, 2.) r.t., overnight 8: 99 percent / Bu4NF / acetonitrile; tetrahydrofuran / 4 h / 70 °C 9: 85.5 percent / CH2Cl2 / 24 h / Ambient temperature 10: 2 M HCl / ethanol / 30 h / Heating View Scheme

Upstream product

• 3587-60-8 Benzyloxymethyl chloride 
• 39939-07-6 5-(benzyloxymethyl)cyclopentadiene 
• 542-92-7 cyclopenta-1,3-diene 
• 4984-82-1 sodium cyclopentadienylide 
• 191480-69-0 (3R,4S)-4-(phenylmethoxy)-3-[(phenylmethoxy)methyl]cyclopent-1-ene 
• 110567-21-0 (1S,2R)-2-(benzyloxymethyl)-1-hydroxy-3-cyclopentene 
• 100-39-0 benzyl bromide 
• 117641-39-1 (2R,3S)-2-benzyloxymethyl-6-oxabicyclo<3.1.0>hexan-3-ol 

Downstream Products

• 114071-50-0 (1S,2S,3S,5S)-5-[2-Amino-6-(2-methoxy-ethoxy)-purin-9-yl]-3-benzyloxy-2-benzyloxymethyl-cyclopentanol 
• 110567-23-2 (1S,2S,3S,5S)-5-azido-3-(benzyloxy)-2-(benzyloxymethyl)cyclopentanol 
• 117641-40-4 (1R,2R,3R,4S)-2-Azido-4-benzyloxy-3-benzyloxymethyl-cyclopentanol 
• 114071-48-6 [1S-(1α,2β,3α,4β)]-1-[2-Hydroxy-4-(phenyl-methoxy)-3-[(phenylmethoxy)methyl]cyclopentyl]-2,4(1H,3H)-pyrimidinedione 
• 114071-49-7 1-(3',5'-di-O-benzyl-2'-deoxy-6'-hydroxy-6'-carba-β-D-ribofuranosyl)thymine 
• 160860-62-8 (1S,2R,3R,4R)-1-Benzyloxy-2-benzyloxymethyl-4-cyano-3-hydroxycyclopentane 
• 142217-96-7 [1S-(1α,2β,3α,5β)]-5-(6-amino-9H-purin-9-yl)-3-(phenylmethoxy)-2-[(phenylmethoxy)methyl]cyclopentanol 
• 142217-77-4 [1S-(1α,2β,3α,5β)]-5-(2-amino-6-benzyloxy-9H-purin-9-yl)-3-benzyloxy-2-(benzyloxy)methyl-cyclopentanol 
• 114884-15-0 1-((1R,3S,4R)-3-hydroxy-4-(hydroxymethyl)cyclopentyl)-5-methylpyrimidine-2,4(1H,3H)-dione 
• 170453-02-8 (1S,3S,4R,5S)-3-Benzyloxy-4-benzyloxymethyl-1-aminobicyclo<3.1.0>hexane 
• 170452-98-9 (3R,4S)-1-Cyano-4-benzyloxy-3-benzyloxymethylcyclopentene 
• 170453-00-6 (1S,3S,4R,5S)-3-Benzyloxy-4-benzyloxymethyl-1-cyanobicyclo<3.1.0>hexane 
• 190195-74-5 (1S,3S,4R,5S)-3-Benzyloxy-4-benzyloxymethylbicyclo<3.1.0>hexane-1-carboxylic acid 
• 170452-99-0 (3aR,4R,5S,6aR)-4-Benzyloxymethyl-5-benzyloxy-6a-cyano-3,3a,4,5,6,6a-hexahydrocyclopentapyrazole 

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