32233-40-2

Basic information

• Product Name: (-)-Corey lactone diol
• Synonyms: (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one;(-)-Core\/ lactone diol;COREY LACTONE DIOL;(3AR,4S,5R,6AS)-(-)-HEXAHYDRO-5-HYDROXY-4-(HYDROXYMETHYL)-2H-CYCLOPENT A[B]FURAN-2-ONE;(3AR,4S,5R,6AS)-HEXAHYDRO-5-HYDROXY-4-(HYDROXYMETHYL)-2H-CYCLOPENTA[B]FURAN-2-ONE;(-)-6BETA-HYDROXYMETHYL-7ALPHA-HYDROXY-CIS-2-OXABICYCLO[3.3.0]OCTAN-3-ONE;(3AR,4S,5R,6AS)-(-)-HEXAHYDRO-5-HYDROXY- 4-HOCH2-2H-CYCLOPENTA(B)FURAN-2-ONE, 98%;Hexahydro-5-hydroxy-4-(hydroxymethyl)-2H-cyclopenta[b]furan-2-one.
• CAS NO: 32233-40-2
• Molecular Formula: C₈H₁₂O₄
• Molecular Weight: 172.18
• EINECS: 1308068-626-2
• Product Categories: Prostaglandins;Latanoprost;API
• Mol File: 32233-40-2.mol
• Article Data: 28

Chemical Properties

• Melting Point: 117-119 °C(lit.)
• Boiling Point: 262.49°C (rough estimate)
• Flash Point: 172.9 °C
• Appearance: White to beige-brown/Crystalline Powder or Crystals
• Density: 1.2104 (rough estimate)
• Vapor Pressure: 2.63E-08mmHg at 25°C
• Refractive Index: 1.4455 (estimate)
• Storage Temp.: -20°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 14.36±0.40(Predicted)
• CAS DataBase Reference: (-)-Corey lactone diol(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-Corey lactone diol(32233-40-2)
• EPA Substance Registry System: (-)-Corey lactone diol(32233-40-2)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 32233-40-2(Hazardous Substances Data)

Usage

Chemical Properties

white to beige-brown cryst. powder or crystals

Uses

Different sources of media describe the Uses of 32233-40-2 differently. You can refer to the following data:
1. (-)-Corey Lactone Diol is an intermediate of Iloprost (I267300) and shows inhibitory activity towards β-lactamase. Iloprost (I267300) is a synthetic analogue of Prostacyclin (PGI2) used to treat pulmo nary arterial hypertension (PAH), scleroderma, Raynaud's phenomenon and ischemia.
2. (-)-Corey Lactone Diol is an intermediate of Iloprost (I267300) and shows inhibitory activity towards β-lactamase. Iloprost (I267300) is a synthetic analogue of Prostacyclin (PGI2) used to treat pulmonary arterial hypertension (PAH), scleroderma, Raynaud''s phenomenon and ischemia.

InChI:InChI=1/C8H12O4/c9-3-5-4-1-8(11)12-7(4)2-6(5)10/h4-7,9-10H,1-3H2/t4-,5-,6-,7+/m1/s1

Synthetic route

(3aR,4S,5R,6aS)-4-((tert-butyldimethylsilyloxy)methyl)-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one (58707-50-9, 72777-85-6, 81203-78-3, 65025-94-7) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With hydrogen; palladium on activated charcoal In dichloromethane at 20℃; for 0.833333h; atmospheric pressure;	99%
Multi-step reaction with 2 steps 1: 90 percent / PPTS / 1,2-dichloro-ethane / 2 h / Ambient temperature 2: 3,4-Dihydro-2H-pyran / TsOH View Scheme

(1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one (39746-00-4) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
Stage #1: (1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one With sodium methylate In methanol at 20℃; for 1.5h; Stage #2: With hydrogenchloride In 1,4-dioxane; methanol at 20℃; pH=3 - 4;	97%
With sodium methylate In methanol at 20℃; for 2h;	95%

(1S,5R,6R,7R)-6-<<(tert-butyldimethylsilyl)oxy>methyl>-7-<(tert-butyldimethylsilyl)oxy>-2-oxabicyclo<3.3.0>octane-3-one (117624-93-8) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With copper(ll) sulfate pentahydrate In methanol at 100℃; for 0.25h; Microwave irradiation;	96%
With cerium (IV) sulfate tetrahydrate In methanol at 60℃; for 12h;	96%
With aluminium(III) chloride hexahydrate In methanol at 100℃; for 0.25h; Solvent; Microwave irradiation; Sealed tube; chemoselective reaction;	95%

(1S,5R,6R,7R)-(-)-2-oxa-6-(hydroxymethyl)-7-acetoxybicyclo<3.3.0>-octan-3-one (26054-65-9) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With Amberlite IR 120 resin In methanol at 70℃; for 8h;	86%

(-)-Corey lactone 5-(4-phenylbenzoate) (31752-99-5) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With potassium carbonate In methanol; dichloromethane for 3h; Ambient temperature;	85%
Multi-step reaction with 4 steps 1: 94 percent / imidazole / dimethylformamide / 1 h / Ambient temperature 2: 65 percent / CH3ONa / methanol / 1.33 h / Ambient temperature 3: 90 percent / PPTS / 1,2-dichloro-ethane / 2 h / Ambient temperature 4: 3,4-Dihydro-2H-pyran / TsOH View Scheme

Biphenyl-4-carboxylic acid (3aR,4S,5R,6aS)-5-hydroxy-2-oxo-hexahydro-cyclopenta[b]furan-4-ylmethyl ester → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With potassium carbonate In tetrahydrofuran; methanol for 4h; Ambient temperature;	83%

(3aR,4S,5R,6aS)-5-(acetyloxy)-4-[(acetyloxy)methyl]hexahydro-2H-cyclopenta[b]furan-2-one (62939-82-6) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With Amberlite IR 120 resin In methanol at 70℃; for 8h;	82%
With hydrogenchloride In methanol; water for 4h; Reflux;	82.1%
With DBN In methanol at 20℃; for 12h;
With methanol at 25 - 65℃;	28 g

(1S,5R,6R,7R)-(-)-6-acetoxymethyl-7-hydroxy-2-oxabicyclo<3.3.0>octan-3-one (57930-46-8) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With Amberlite IR 120 resin In methanol at 70℃; for 8h;	82%
With resin Wofatit SBW (OH-) In methanol for 2h; Ambient temperature;	79%

formaldehyd (50-00-0) + (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one (26054-46-6) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
Stage #1: formaldehyd; (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one With formic acid; sulfuric acid at 80℃; for 24h; Stage #2: With potassium carbonate In methanol at 0 - 20℃; for 2h;	79%

(4aS,4bR,7aS,8aR)-Hexahydro-furo[3',2':3,4]cyclopenta[1,2-d][1,3]dioxin-6-one (109122-52-3) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + 1,1-dimethoxyethane (534-15-6)

Conditions	Yield
With toluene-4-sulfonic acid In methanol at 75 - 80℃; for 4h;	A 78% B n/a

(E)-(4S,6R)-4,6-Dihydroxy-6-((S)-2-thioxo-[1,3]dioxolan-4-yl)-hex-2-enoic acid methyl ester (159812-78-9) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + (3aR,4R,5R,6aS)-(-)-5-hydroxy-4-hydroxymethyl-hexahydro-cyclopenta[b]furan-2-one (159812-79-0) + (2S,6S,8R,9R)-8-Hydroxy-5,11,12-trioxa-tricyclo[7.2.1.02,6]dodecan-4-one + ((1R,2R,4S,5R)-2,4-Dihydroxy-7,9-dioxa-bicyclo[4.2.1]non-5-yl)-acetic acid methyl ester

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene Heating; Further byproducts given;	A 19% B 44% C 13% D 8%
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene Heating;	A 19% B 40% C n/a D n/a

(E)-(4S,6R)-4,6-Dihydroxy-6-((S)-2-thioxo-[1,3]dioxolan-4-yl)-hex-2-enoic acid methyl ester (159812-78-9) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + (3aR,4R,5R,6aS)-(-)-5-hydroxy-4-hydroxymethyl-hexahydro-cyclopenta[b]furan-2-one (159812-79-0) + (2S,6S,8R,9R)-8-Hydroxy-5,11,12-trioxa-tricyclo[7.2.1.02,6]dodecan-4-one + (E)-(4S,6R,7S)-4,6,7,8-Tetrahydroxy-oct-2-enoic acid methyl ester

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene Heating; Further byproducts given;	A 19% B 44% C 13% D 2%

(E)-(4S,6R)-4,6-Dihydroxy-6-((S)-2-thioxo-[1,3]dioxolan-4-yl)-hex-2-enoic acid methyl ester (159812-78-9) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + (3aR,4R,5R,6aS)-(-)-5-hydroxy-4-hydroxymethyl-hexahydro-cyclopenta[b]furan-2-one (159812-79-0) + (2S,6S,8R,9R)-8-Hydroxy-5,11,12-trioxa-tricyclo[7.2.1.02,6]dodecan-4-one + (S)-4-[(R)-1-Hydroxy-2-((R)-5-oxo-tetrahydro-furan-2-yl)-ethyl]-[1,3]oxathiolan-2-one

Conditions	Yield
With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride In benzene Heating; Further byproducts given;	A 19% B 44% C 13% D 1%

(1SR, 5RS, 6RS, 7RS)-7-acetoxy-6-acetoxymethyl-2-oxabicyclo<3.3.0>octan-3-one (90529-18-3) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + (1S,5R,6R,7R)-(-)-2-oxa-6-(hydroxymethyl)-7-acetoxybicyclo<3.3.0>-octan-3-one (26054-65-9) + <3aS(3aα,4α,5β,6aα)>-(+)-5-hydroxy-4-hydroxymethyl-hexahydro-2H-cyclopentafuran-2-one (76704-05-7) + (3aS,4R,5S,6aR)-5-acetoxy-4-(hydroxymethyl)hexahydro-2H-cyclopentafuran-2-one (125226-81-5)

Conditions	Yield
With sodium hydroxide; Soerensen phosphate buffer In methanol at 36℃; for 24h; subtilisin DY; Further byproducts given. Yields of byproduct given;	A n/a B n/a C 20% D n/a
With sodium hydroxide; Soerensen phosphate buffer In methanol at 36℃; for 24h; subtilisin DY; Further byproducts given. Yields of byproduct given;	A 16% B n/a C n/a D n/a

3,4-dihydro-2H-pyran (110-87-2) + (3aR,4S,5R,6aS)-4-({[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl)-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-one (65025-95-8) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + (1S,5R,6S,7R)-7-(tetrahydropyran-2-yl)oxy-6-(tetrahydropyran-2-yl)oxymethyl-2-oxabicyclo[3.3.0]octan-3-one (67788-45-8)

Conditions	Yield
toluene-4-sulfonic acid Yields of byproduct given;	A n/a B 17%

(3aR,4S,5R,6aS)-4-({[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl)-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-one (65025-95-8) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + (1S,5R,6S,7R)-7-(tetrahydropyran-2-yl)oxy-6-(tetrahydropyran-2-yl)oxymethyl-2-oxabicyclo[3.3.0]octan-3-one (67788-45-8)

Conditions	Yield
With 3,4-dihydro-2H-pyran; toluene-4-sulfonic acid Yield given;	A n/a B 17%

formaldehyd (50-00-0) + (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one (26054-46-6) + acetic anhydride (108-24-7) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + (4aS,4bR,7aS,8aR)-Hexahydro-furo[3',2':3,4]cyclopenta[1,2-d][1,3]dioxin-6-one (109122-52-3)

Conditions	Yield
With sodium hydroxide; sulfuric acid 1) 70 to 80 deg C, 20 h, sealed vessel, 2) 60 to 65 deg C, 40 h, sealed vessel, 3) RT, 20 h; Multistep reaction;

Formic acid (3aR,4S,5R,6aS)-4-formyloxymethyl-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester (130325-32-5) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With sodium methylate In methanol
With sodium In methanol at 0℃; for 0.5h;	6.2 g

(3aR,4S,5R,6aS)-4-(hydroxymethyl)-5-((tetrahydro-2H-pyran-2-yl)oxy)hexahydro-2H-cyclopenta[b]furan-2-one (69222-61-3) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran at 25℃; Yield given;

(1SR, 5RS, 6RS, 7RS)-7-acetoxy-6-acetoxymethyl-2-oxabicyclo<3.3.0>octan-3-one (90529-18-3) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + (1S,5R,6R,7R)-(-)-2-oxa-6-(hydroxymethyl)-7-acetoxybicyclo<3.3.0>-octan-3-one (26054-65-9) + <3aS(3aα,4α,5β,6aα)>-(+)-5-hydroxy-4-hydroxymethyl-hexahydro-2H-cyclopentafuran-2-one (76704-05-7) + (3aS,4R,5S,6aR)-5-acetoxy-4-(hydroxymethyl)hexahydro-2H-cyclopentafuran-2-one (125226-81-5) + (1S,5R,6R,7R)-(-)-6-acetoxymethyl-7-hydroxy-2-oxabicyclo<3.3.0>octan-3-one (57930-46-8) + (1R,5S,6S,7S)-(+)-6-acetoxymethyl-7-hydroxy-2-oxabicyclo<3.3.0>octan-3-one (125226-80-4)

Conditions	Yield
With sodium hydroxide In methanol at 36℃; for 24h; Product distribution; subtilisin DY, Soerensen phosphate buffer pH 7, further solvents, further enzymes;

2-oxa-3-oxo-6-syn-hydroxymethyl-7-anti-acetoxy-cis-bicyclo[3,3,0]octane (51705-34-1, 39648-25-4) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + <3aS(3aα,4α,5β,6aα)>-(+)-5-hydroxy-4-hydroxymethyl-hexahydro-2H-cyclopentafuran-2-one (76704-05-7)

Conditions	Yield
With Wofatit SBW In methanol for 2h; Ambient temperature; Title compound not separated from byproducts;

2-oxa-3-oxo-6-syn-acetoxymethyl-7-anti-hydroxy-cis-bicyclo[3,3,0]octane (134732-93-7) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + <3aS(3aα,4α,5β,6aα)>-(+)-5-hydroxy-4-hydroxymethyl-hexahydro-2H-cyclopentafuran-2-one (76704-05-7)

Conditions	Yield
With Wofatit SBW In methanol for 2h; Ambient temperature; Title compound not separated from byproducts;

(4aR,5S,7R,7aS)-5,7-Bis-(tert-butyl-dimethyl-silanyloxy)-hexahydro-cyclopenta[c]pyran-3-one → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran Ambient temperature;

(1S,2S,6R,8S)-10,10-dimethyl-5,9,11-trioxatricyclo[6.4.0.02,6]dodecan-4-one (315716-34-8) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
With Dowex 50wX8 In tetrahydrofuran; water at 20℃; for 3h;

6-oxabicyclo[3.1.0]hex-2-ene (7129-41-1) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions

Yield

Multi-step reaction with 8 steps 1: 70 percent / tetrahydrofuran / 1.5 h / -78 - 0 °C 2: 0.95 g / 30percent H2O2, 30 percent KOH / ethanol / 1.) 45 deg C, 1 h, 2.) reflux, 6 h 3: 91 percent / HCL / 0.67 h 4: 80 percent / pyridine / 1 h / 0 °C 5: 94 percent / 5percent NaOH / tetrahydrofuran / 24 h / 0 °C 6: 92 percent / conc. sulfuric acid / 1.) 80 deg C, 5 h, 2.) RT, 12 h 7: 6.2 g / sodium / methanol / 0.5 h / 0 °C View Scheme

(-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one (26054-46-6) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / conc. sulfuric acid / 1.) 80 deg C, 5 h, 2.) RT, 12 h 2: 6.2 g / sodium / methanol / 0.5 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: H2SO4 2: MeONa / methanol View Scheme
Multi-step reaction with 2 steps 1: 9.5 percent / glacial acetic acid, sulfuric acid / 24 h / 75 - 80 °C 2: 78 percent / p-toluenesulfonic acid / methanol / 4 h / 75 - 80 °C View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid / 24 h / 50 - 80 °C / Sealed tube 2: DBN / methanol / 12 h / 20 °C View Scheme

(-)-trans-2-carboxymethylcyclopent-3-en-1-ol (49826-03-1) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: 91 percent / HCL / 0.67 h 2: 80 percent / pyridine / 1 h / 0 °C 3: 94 percent / 5percent NaOH / tetrahydrofuran / 24 h / 0 °C 4: 92 percent / conc. sulfuric acid / 1.) 80 deg C, 5 h, 2.) RT, 12 h 5: 6.2 g / sodium / methanol / 0.5 h / 0 °C View Scheme

methyl 2R-methylsulfonyloxy-4-cyclopentene-1R-acetate (49826-01-9) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / 5percent NaOH / tetrahydrofuran / 24 h / 0 °C 2: 92 percent / conc. sulfuric acid / 1.) 80 deg C, 5 h, 2.) RT, 12 h 3: 6.2 g / sodium / methanol / 0.5 h / 0 °C View Scheme

(-)-trans-2-methoxycarbonylmethylcyclopent-3-en-1-ol (49825-99-2) → (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 80 percent / pyridine / 1 h / 0 °C 2: 94 percent / 5percent NaOH / tetrahydrofuran / 24 h / 0 °C 3: 92 percent / conc. sulfuric acid / 1.) 80 deg C, 5 h, 2.) RT, 12 h 4: 6.2 g / sodium / methanol / 0.5 h / 0 °C View Scheme

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + trityl chloride (76-83-5) → (-)-7α-hydroxy-6β-triphenylmethoxymethyl-cis-2-oxabicyclo<3.3.0>octan-3-one (62939-85-9)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;	100%
With pyridine In dichloromethane	93%
With pyridine at 20℃; for 48h;	87%
In pyridine at 20℃; for 48h; Substitution;	87%
With pyridine at 20℃; for 12h; Temperature; Large scale;

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + triisopropylsilyl chloride (13154-24-0) → [(3aR,4S,5R,6aS)-hexahydro-5-hydroxy-4(triisopropylsilyloxymethyl)-2H-cyclopenta[b]furan-2-one] (1236109-24-2)

Conditions	Yield
With 1H-imidazole In dichloromethane for 15h;	100%
Stage #1: (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one; triisopropylsilyl chloride With 1H-imidazole In dichloromethane for 15h; Stage #2: With hydrogenchloride In dichloromethane; water at 0℃; pH=3 - 4;	100%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + tert-butyldimethylsilyl chloride (18162-48-6) → (1S,5R,6R,7R)-6-<<(tert-butyldimethylsilyl)oxy>methyl>-7-<(tert-butyldimethylsilyl)oxy>-2-oxabicyclo<3.3.0>octane-3-one (117624-93-8)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide for 3h; Inert atmosphere;	100%
With 1H-imidazole In dichloromethane at 0 - 40℃; for 24h; Inert atmosphere;	95%
With 1H-imidazole; dmap In dichloromethane at 0 - 30℃; for 16h;	340 g
With 1H-imidazole In dichloromethane at 40℃; Inert atmosphere;	23 g

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + triisopropylsilyl trifluoromethanesulfonate (80522-42-5) → [(3aR,4S,5R,6aS)-hexahydro-5-hydroxy-4(triisopropylsilyloxymethyl)-2H-cyclopenta[b]furan-2-one] (1236109-24-2)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere;	100%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + triethylsilyl chloride (994-30-9) → (-)-7α-triethylsilyloxy-6β-triethylsilyloxymethyl-cis-2-oxabicyclo<3.3.0>octan-3-one (128948-09-4)

Conditions	Yield
With pyridine at 60℃; for 1h;	97%
With pyridine at 65℃; for 4h;	94.55%
With pyridine at 60℃; for 1h;	93%
With pyridine at 60℃; for 1h;	93%
With 1H-imidazole In N,N-dimethyl-formamide at 5℃; for 4h; Inert atmosphere;

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + tert-butyldimethylsilyl chloride (18162-48-6) → (3aR,4S,5R,6aS)-4-((tert-butyldimethylsilyloxy)methyl)-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one (58707-50-9, 72777-85-6, 81203-78-3, 65025-94-7)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at 0 - 10℃; for 2h;	96.3%
With 1H-imidazole In dichloromethane at 20℃;	94.5%
With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 1h;	89%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) → Corey aldehyde (62961-72-2)

Conditions	Yield
With oxalyl dichloride In dichloromethane; dimethyl sulfoxide at -78℃; for 1.03333h; Reagent/catalyst; Solvent; Temperature;	95%
With oxalyl dichloride In dichloromethane; dimethyl sulfoxide at -78℃; for 1h; Reagent/catalyst; Solvent; Temperature;	95%
With oxalyl dichloride; triethylamine In dimethyl sulfoxide

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + 4-biphenyl-carboxylic acid chloride (14002-51-8) → (-)-Corey lactone 5-(4-phenylbenzoate) (31752-99-5)

Conditions	Yield
Stage #1: (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one With pyridine; trityl chloride at 20℃; for 12h; Large scale; Stage #2: 4-biphenyl-carboxylic acid chloride at 30℃; for 4.5h; Temperature; Large scale;	93.45%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + triethylsilyl chloride (994-30-9) → C14H26O4Si

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20 - 30℃; for 2h; Temperature; Solvent; Reagent/catalyst;	92%

methanol (67-56-1) + (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) → methyl (1R,2R,3R,5R)-(5-chloro-2-chloromethyl-3-hydroxycyclopentyl)acetate

Conditions	Yield
With thionyl chloride at 0 - 20℃; for 7h;	92%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + N,N-diethyl-1,1,1-trimethylsilanamine (996-50-9) → 7α-hydroxy-6β-hydroxymethylene-2-oxabicyclo<3.3.0>octan-3-one bistrimethylsilyl ether (118457-23-1)

Conditions	Yield
at 145℃; for 1h;	90%

vinyl acetate (108-05-4) + (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) → (1S,5R,6R,7R)-(-)-6-acetoxymethyl-7-hydroxy-2-oxabicyclo<3.3.0>octan-3-one (57930-46-8)

Conditions	Yield
With ALPS at 40℃; for 24h;	90%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + t-butyldimethylsiyl triflate (69739-34-0) → (1S,5R,6R,7R)-6-<<(tert-butyldimethylsilyl)oxy>methyl>-7-<(tert-butyldimethylsilyl)oxy>-2-oxabicyclo<3.3.0>octane-3-one (117624-93-8)

Conditions	Yield
With 2,6-dimethylpyridine In dichloromethane at -20 - 20℃; Inert atmosphere;	89.4%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + p-Anisaldehyde dimethyl acetal (2186-92-7) → C16H18O5 (1210039-33-0)

Conditions	Yield
4-methoxybenzoic acid In toluene at 120℃; for 3h; Dean-Stark apparatus;	87%

3,4-dihydro-2H-pyran (110-87-2) + (3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) → (1S,5R,6S,7R)-7-(tetrahydropyran-2-yl)oxy-6-(tetrahydropyran-2-yl)oxymethyl-2-oxabicyclo[3.3.0]octan-3-one (67788-45-8)

Conditions	Yield
toluene-4-sulfonic acid In dichloromethane for 1.5h; Ambient temperature;	84%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + tert-butylchlorodiphenylsilane (58479-61-1) → (3aR,4S,5R,6aS)-hexahydro-5-hydroxy-4-[(tert-butyldiphenylsilyloxy)methyl]-2H-cyclopenta[b]furan-2-one (84786-80-1)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at -40℃; for 2h;	84%
With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 2h;

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + tert-butyldimethylsilyl chloride (18162-48-6) → (3aR,4S,5R,6aS)-5-[(tert-butyldimethylsilyl)oxy]-4-(hydroxymethyl)-hexahydro-2H-cyclopenta[b]furan-2-one (39968-95-1)

Conditions	Yield
With 1H-imidazole In dichloromethane at 20℃; for 8h; Reagent/catalyst;	83%
With 1H-imidazole In dichloromethane at 20℃; for 8h;	82%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + benzoyl chloride (98-88-4) → ((3aS,4R,5S,6aR)-5-(benzoyloxy)-2-oxohexahydro-2H-cyclopenta[b]furan-4-yl)methyl benzoate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 0.5h; Inert atmosphere; enantioselective reaction;	80%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + tert-butyldimethylsilyl chloride (18162-48-6) → (3aR,4S,5R,6aS)-4-((tert-butyldimethylsilyloxy)methyl)-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one (58707-50-9, 72777-85-6, 81203-78-3, 65025-94-7) + (1S,5R,6R,7R)-6-<<(tert-butyldimethylsilyl)oxy>methyl>-7-<(tert-butyldimethylsilyl)oxy>-2-oxabicyclo<3.3.0>octane-3-one (117624-93-8)

Conditions	Yield
With dmap; triethylamine In dichloromethane 1.) -20 deg C, 1.5 h, 2.) room temperature, 16 h;	A 76% B 4%

(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one (32233-40-2) + p-toluenesulfonyl chloride (98-59-9) → (3aR,4S,5R,6aS)-5-p-toluenesulfoxy-4-[(p-toluenesulfoxy)methyl]hexahydrocyclopenta[b]furan-2-one (1063693-23-1)

Conditions	Yield
With pyridine at 0 - 20℃; for 3h;	73%

Upstream product

• 50-00-0 formaldehyd 
• 26054-46-6 (-)-(1S,5R)-2-oxabicyclo[3.3.0]oct-6-en-3-one 
• 108-24-7 acetic anhydride 
• 51705-34-1 2-oxa-3-oxo-6-syn-hydroxymethyl-7-anti-acetoxy-cis-bicyclo[3,3,0]octane 
• 134732-93-7 2-oxa-3-oxo-6-syn-acetoxymethyl-7-anti-hydroxy-cis-bicyclo[3,3,0]octane 
• 110-87-2 3,4-dihydro-2H-pyran 
• 65025-95-8 (3aR,4S,5R,6aS)-4-({[dimethyl(2-methyl-2-propanyl)silyl]oxy}methyl)-5-(tetrahydro-2H-pyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-one 
• 117624-93-8 (1S,5R,6R,7R)-6-<<(tert-butyldimethylsilyl)oxy>methyl>-7-<(tert-butyldimethylsilyl)oxy>-2-oxabicyclo<3.3.0>octane-3-one 
• 98-00-0 (2-furyl)methyl alcohol 
• 59995-47-0 4-Hydroxycyclopent-2-enone 
• 29783-26-4 cis-4-cyclopentene-1,3-diol 
• 60176-77-4 (1S,4R)-4-hydroxy-2-cyclopentenyl acetate 
• 34638-25-0 2-oxabicyclo[3.3.0]oct-6-en-3-one 
• 5307-99-3 (+/-)-7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one 

Downstream Products

• 105394-12-5 Toluene-4-sulfonic acid (3aR,4S,5R,6aS)-5-hydroxy-2-oxo-hexahydro-cyclopenta[b]furan-4-ylmethyl ester 
• 58707-50-9 (3aR,4S,5R,6aS)-4-((tert-butyldimethylsilyloxy)methyl)-5-hydroxyhexahydro-2H-cyclopenta[b]furan-2-one 
• 84786-80-1 (3aR,4S,5R,6aS)-hexahydro-5-hydroxy-4-[(tert-butyldiphenylsilyloxy)methyl]-2H-cyclopenta[b]furan-2-one 
• 60325-46-4 Sulprostone 
• 54276-21-0 (+)-cloprostenol 
• 51638-93-8 7α-hydroxy-6β-(3'-hydroxy-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one 
• 871669-32-8 7α-hydroxy-6β-(3'-oxo-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one 
• 53872-62-1 Cloprostenol 
• 871669-30-6 7α-trimethylsilyloxy-6β-(3'-oxo-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one 
• 127718-28-9 7α-trimethylsilyloxy-6β-(3'α-trimethylsilyloxy-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-ol 
• 127702-12-9 7α-trimethylsilyloxy-6β-(3'α-trimethylsilyloxy-4'-phenoxy-1'E-butenyl)-2-oxabicyclo<3.3.0>octan-3-one 
• 79172-00-2 N-(methanesulfonyl)-16-phenox-ω-tetranor-PGF_2α-carboxamide 
• 127718-29-0 N-{(Z)-7-[(1R,2R,3R,5S)-5-Hydroxy-2-((E)-(R)-4-phenoxy-3-trimethylsilanyloxy-but-1-enyl)-3-trimethylsilanyloxy-cyclopentyl]-hept-5-enoyl}-methanesulfonamide 
• 89560-44-1 (3aR,4R,5R,6aS)-4-[(E)-4-(3-Chloro-phenoxy)-3-hydroxy-but-1-enyl]-hexahydro-cyclopenta[b]furan-2,5-diol 

Relevant articles and documents

HPLC and SFC enantioseparation of (±)-Corey lactone diol: Impact of the amylose tris-(3,5-dimethylphenylcarbamate) coating amount on chiral preparation

As an important intermediate of prostaglandins and entecavir, optically pure Corey lactone diol (CLD) has great value in the pharmaceutical industry. In this work, the enantioseparation of (±)-CLD was evaluated using high-performance liquid (HPLC) and supercritical fluid chromatography (SFC). In HPLC, the separations of CLD enantiomers on polysaccharide-based chiral stationary phases with both normal phase and polar organic phase were screened. And the conditions for the enantioseparation were optimized in HPLC and SFC, including the selection of mobile phase, temperature, back-pressure, and other conditions. More important, it was found that the chiral resolutions were greatly enhanced by the increase of the coating amount of ADMPC (amylose tris-(3,5-dimethylphenylcarbamate)) under both HPLC and SFC conditions, which can lead to the increase of the productivity and the decrease of the solvent consumption. The preparations of optically pure CLD were evaluated on a semi-preparative (2?×?25?cm) column packed with 30% ADMPC-coated CSP under HPLC and SFC conditions. Preparative performances in terms of kkd are 1.536?kg racemate/kg CSP/day and 1.248?kg racemate/kg CSP/day in HPLC and SFC, respectively.

Preparation method corey lactone diol

The invention provides a preparation method of corey lactone diol, which has the advantages of easily available raw materials. The method has the characteristics of mild reaction conditions, simple operation, simple synthetic route, high chemical yield, low cost and the like, and is suitable for industrial production.

A synthesis method of the branch stands lactone diol

The invention discloses a method for the branch stands lactone diol (( -) - Corey lactone diol) synthetic method, synthesis method of the invention is to dicyclopentadiene as raw materials, by depolymerization, cyclization, oxidation, dechlorination, open-loop, split, Prins reaction, hydrolysis reaction to obtain the target product. The invention discloses a synthetic route, raw material economic, high separation efficiency, and is suitable for industrial production.