86087-23-2

Basic information

• Product Name: (S)-(+)-3-Hydroxytetrahydrofuran
• Synonyms: (S)-TETRAHYDROFURAN-3-OL;(S)-(+)-TETRAHYDRO-3-FURANOL;(S)-(+)-3-HYDROXY TETAHYDRO FURAN;(S)-(-)-3-HYDROXY TETRAHYDRO FURAN;(S)-(+)-3-HYDROXYTETRAHYDROFURAN;(S)-3-HYDROXYTETRAHYDROFURAN;(S)-(+)-3-HYDROXYTETRAHYDROFURANE;3-FURANOL, TETRAHYDRO-, (S)
• CAS NO: 86087-23-2
• Molecular Formula: C4H8O2
• Molecular Weight: 88.11
• EINECS: 1308068-626-2
• Product Categories: Alcohols, Hydroxy Esters and Derivatives;Chiral Compounds;Starting Raw Materials & Intermediates;Small molecule;Tetrahydrofuran Series;Chiral Reagents;Furans;Chiral Building Blocks;Simple Alcohols (Chiral);Synthetic Organic Chemistry;Afatinib intermediate
• Mol File: 86087-23-2.mol
• Article Data: 28

Chemical Properties

• Boiling Point: 80 °C15 mm Hg(lit.)
• Flash Point: 175 °F
• Appearance: Clear colorless to pale yellow/Liquid
• Density: 1.103 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.255mmHg at 25°C
• Refractive Index: n20/D 1.45(lit.)
• Storage Temp.: Refrigerator
• Solubility: Chloroform, Methanol (Slightly)
• PKA: 14.49±0.20(Predicted)
• Water Solubility: soluble
• Stability: Stable. Combustible. Incompatible with strong oxidizing agents.
• BRN: 4652609
• CAS DataBase Reference: (S)-(+)-3-Hydroxytetrahydrofuran(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(+)-3-Hydroxytetrahydrofuran(86087-23-2)
• EPA Substance Registry System: (S)-(+)-3-Hydroxytetrahydrofuran(86087-23-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39
• RIDADR: NA 1993 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 86087-23-2(Hazardous Substances Data)

Usage

Chemical Properties

Colourless Liquid

Uses

Different sources of media describe the Uses of 86087-23-2 differently. You can refer to the following data:
1. Amprenavir and Fosamprenavir intermediate
2. (S)-(+)-3-Hydroxytetrahydrofuran is a useful reagent for the preparation of pyrazolo triazin ylamine derivatives as adenosine receptor antagonists.

InChI:InChI=1/C4H8O2/c5-4-1-2-6-3-4/h4-5H,1-3H2/t4-/m0/s1

Synthetic route

(3S)-4-chloro-1,3-butanediol (139013-68-6) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In methanol; water	99.8%
With potassium hydroxide In methanol at 40℃; for 4h; Reagent/catalyst;	97%
In anhydrous ethylene glycol dimethyl ether at 110℃; for 5h; Product distribution / selectivity;	90%

4-chloro-3-hydroxy-1-butanol (145873-44-5) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With hydrogenchloride In water at 50℃; for 4h; Solvent; Reagent/catalyst;	94.6%

(S)-3-(4-Methoxy-benzyloxy)-tetrahydro-furan → ethyl p-methoxybenzyl sulfide (83318-92-7) + (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With aluminium trichloride; ethanethiol In dichloromethane for 5h; Ambient temperature;	A n/a B 93%

(S)-1,2,4-butanetriol (42890-76-6) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With toluene-4-sulfonic acid (3a preparation above 7a);	87%
toluene-4-sulfonic acid In PEG-400 at 120 - 160℃; under 10 Torr; for 12h; Product distribution / selectivity;	83%
strong acid ion exchange resin (Amberlyst 15, H+ form) In 1,4-dioxane at 90 - 120℃; under 760.051 - 5931.67 Torr; Product distribution / selectivity;	70%
With toluene-4-sulfonic acid
With toluene-4-sulfonic acid In water at 90℃;	10 g

(S)-tetrahydrofuran-3-yl acetate → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With sodium hydroxide In methanol; water at 20℃; for 3h;	83%

(S)-3-benzyloxytetrahydrofuran → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With palladium on activated charcoal; hydrogen at 40℃;	81.5%

(R)-3-Hydroxytetrahydrofuran (86087-24-3) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
Stage #1: (R)-3-Hydroxytetrahydrofuran With azodicarboxylic acid bis(2-methoxyethyl) ester; 4-diphenylphosphanobenzoic acid In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: With water; sodium hydroxide In tetrahydrofuran at 20℃; stereospecific reaction;	64%

2-(oxiran-2-yl)ethyl 4-methylbenzenesulfonate (115914-74-4) → (S)-3-hydroxytetyrahydrofurane (86087-23-2) + 2-((R)-oxiran-2-yl)ethyl 4-methylbenzenesulfonate

Conditions	Yield
With (S,S)-(salen)cobalt(III)(OAc); water In tetrahydrofuran at 0 - 25℃; for 14h; optical yield given as %ee; enantioselective reaction;	A 48% B 47%

2,3-dihydro-2H-furan (1191-99-7) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
Yield given. Multistep reaction;

2,5-dihydrofuran (1708-29-8) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
Multistep reaction;
Yield given. Multistep reaction;

(S)-3-(trichlorosilyl)tetrahydrofuran → (R)-3-Hydroxytetrahydrofuran (86087-24-3) + (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With potassium fluoride; dihydrogen peroxide; potassium hydrogencarbonate In tetrahydrofuran; methanol for 16h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

4-chloro-3-hydroxy-1-butanol (145873-44-5) → 2,5-dihydrofuran (1708-29-8) + (R)-3-Hydroxytetrahydrofuran (86087-24-3) + (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With hydrogenchloride for 2h; Heating;	A 15 % Chromat. B n/a C n/a
With hydrogenchloride for 2h; Heating; Yields of byproduct given. Title compound not separated from byproducts;	A 15 % Chromat. B n/a C n/a

3-Hydroxytetrahydrofuran (453-20-3) → (R)-3-Hydroxytetrahydrofuran (86087-24-3) + (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With vinyl acetate; Candida antarctica B lipase on carrier C3 In hexane at 37℃; for 0.0833333h; Title compound not separated from byproducts;

(+/-)-tetrahydrofuran-3-yl acetate (27999-96-8) → (R)-3-Hydroxytetrahydrofuran (86087-24-3) + (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With sodium phosphate buffer; esterase B from Candida antarctica In water at 37℃; for 1h; pH=7.3; Product distribution;

(2S)-2-tert-Butoxy-1,4-butanediol (167971-73-5) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With toluene-4-sulfonic acid at 18 - 77℃; under 12.5 - 15 Torr;

3-Hydroxytetrahydrofuran (453-20-3) + vinyl acetate (108-05-4) → (R)-3-Hydroxytetrahydrofuran (86087-24-3) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) + (R)-tetrahydrofuran-3-yl acetate + (S)-tetrahydrofuran-3-yl acetate

Conditions	Yield
With EL-14 lipase In hexane at 4℃; for 16h; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;

but-3-enyl 4-methylbenzenesulfonate (778-29-0) → (R)-3-Hydroxytetrahydrofuran (86087-24-3) + (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With potassium osmate(VI) dihydrate; methanesulfonamide; water; potassium carbonate; hydroquinidein 1,4-phthalazinediyl diether; potassium hexacyanoferrate(III) In tert-butyl alcohol at 0℃; for 6h; Sharpless asymmetric dihydroxylation; optical yield given as %ee;

(+/-)-tetrahydrofuran-3-yl acetate (27999-96-8) → (S)-3-hydroxytetyrahydrofurane (86087-23-2) + (R)-tetrahydrofuran-3-yl acetate

Conditions	Yield
With crude extract of Escherichia coli DH5α cells containing Bacillus stearothermophilus esterase, D31T/L93F mutant In aq. phosphate buffer at 37℃; for 42h; pH=7.5; Reagent/catalyst; Enzymatic reaction; enantioselective reaction;

tetrahydrofuran-3-one (22929-52-8) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With nicotinamide adenine dinucleotide In aq. phosphate buffer; acetonitrile at 30℃; for 4h; pH=7.4; Kinetics; Reagent/catalyst; Enzymatic reaction; enantioselective reaction;	n/a
With alcohol dehydrogenase fromThermoanaerobacter brockii, A85V/I86L/L294Q mutant; NADP; lysozyme; DNase I In isopropyl alcohol at 30℃; for 16h; Enzymatic reaction; stereoselective reaction;	n/a

C7H18NO2(1+)*Cl(1-) → (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With sodium hydroxide In dimethyl sulfoxide at 170 - 190℃; Reagent/catalyst; Inert atmosphere;

tetrahydrofuran-3-one (22929-52-8) → (R)-3-Hydroxytetrahydrofuran (86087-24-3) + (S)-3-hydroxytetyrahydrofurane (86087-23-2)

Conditions	Yield
With alcohol dehydrogenase fromThermoanaerobacter brockii, A85V/I86L/L294H mutant; NADP; lysozyme; DNase I In isopropyl alcohol at 30℃; for 16h; Enzymatic reaction; stereoselective reaction;	A n/a B n/a
With alcohol dehydrogenase fromThermoanaerobacter brockii, L294C mutant; NADP; lysozyme; DNase I In isopropyl alcohol at 30℃; for 16h; Enzymatic reaction; stereoselective reaction;	A n/a B n/a

di(succinimido) carbonate (74124-79-1) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → 1-({[(3S)-tetrahydro-3-furanyloxy]carbonyl}oxy)-2,5-pyrrolidinedione (138499-08-8)

Conditions	Yield
With triethylamine In acetonitrile at 20℃; for 18h;	100%
With triethylamine In acetonitrile at 20℃; for 18h;	100%
With triethylamine In acetonitrile at 20℃; for 21.5h;	94%

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + 3-cyanocarbonyl-3'-methoxycarbonyl-2,2'-binaphthalene → [2,2']Binaphthalenyl-1,3'-dicarboxylic acid 1-methyl ester 3'-(S)-(tetrahydro-furan-3-yl) ester

Conditions	Yield
With dmap In acetonitrile at 20℃;	100%

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + Carbonic acid (1R,2S)-2-tert-butoxycarbonylamino-1-{[isobutyl-(4-nitro-benzenesulfonyl)-amino]-methyl}-3-phenyl-propyl ester 4-nitro-phenyl ester (229495-94-7) → Carbonic acid (1R,2S)-2-tert-butoxycarbonylamino-1-{[isobutyl-(4-nitro-benzenesulfonyl)-amino]-methyl}-3-phenyl-propyl ester (S)-(tetrahydro-furan-3-yl) ester (229495-71-0)

Conditions	Yield
With triethylamine In 1,4-dioxane for 48h; Heating;	100%

3-hydroxy-5-(4-methanesulfonylphenoxy)benzoic acid methyl ester (752242-45-8) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → C19H20O7S (1001420-25-2)

Conditions	Yield
With 4,4-(dimethyl-1,1-dioxido-1,2,5-thiadiazolidin-2-yl)-triphenyl phosphonium In dichloromethane; toluene at 20℃; for 15h;	100%

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + p-toluenesulfonyl chloride (98-59-9) → toluene-4-sulfonic acid (S)-(tetrahydrofuran-3-yl)ester (112052-11-6)

Conditions	Yield
With 1H-imidazole; dmap In dichloromethane at 20℃; for 16h;	100%
With pyridine	100%
With trimethylamine hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 4h;	99%

(3-fluoro-2-hydroxy-5-nitro-benzyl)-methyl-carbamic acid tert-butyl ester (1037093-11-0) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (R)-tert-butyl 3-fluoro-5-nitro-2-((tetrahydrofuran-3-yl)oxy)benzyl(methyl)carbamate (1508296-65-8)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 16.5h;	100%

trifluoromethylsulfonic anhydride (358-23-6) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (S)-tetrahydrofuran-3-yl trifluoromethanesulfonate

Conditions	Yield
Stage #1: trifluoromethylsulfonic anhydride With N-ethyl-N,N-diisopropylamine In dichloromethane at -78℃; for 0.0833333h; Inert atmosphere; Stage #2: (S)-3-hydroxytetyrahydrofurane In dichloromethane at -78 - 20℃; for 3h; Inert atmosphere;	100%
With pyridine In dichloromethane at -10℃; for 0.5h;

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine (162012-67-1) → 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline

Conditions	Yield
Stage #1: (S)-3-hydroxytetyrahydrofurane With potassium tert-butylate In tetrahydrofuran at 20℃; for 1h; Stage #2: N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine In tetrahydrofuran at 20℃; for 3h;	99.5%
Stage #1: (S)-3-hydroxytetyrahydrofurane With sodium hydride In tetrahydrofuran; mineral oil for 0.75h; Cooling with ice; Stage #2: N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine In tetrahydrofuran at 20℃; for 5h;	99.5%
Stage #1: (S)-3-hydroxytetyrahydrofurane With sodium hydride In tetrahydrofuran; mineral oil for 0.75h; Cooling with ice; Stage #2: N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine In tetrahydrofuran; mineral oil at 20℃; for 5h;	99.5%

4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-fluoroquinazoline + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → 4-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline

Conditions	Yield
Stage #1: (S)-3-hydroxytetyrahydrofurane With sodium hydride In tetrahydrofuran; mineral oil for 0.75h; Cooling with ice; Stage #2: 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-fluoroquinazoline In tetrahydrofuran; mineral oil at 20℃; for 5h;	99.5%

1-(2-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one (1309831-35-3) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → 1-(2-((S)-tetrahydrofuran-3-yloxy)-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one

Conditions	Yield
Stage #1: (S)-3-hydroxytetyrahydrofurane With potassium tert-butylate In tetrahydrofuran at 0℃; for 0.333333h; Inert atmosphere; Stage #2: 1-(2-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one In tetrahydrofuran at 0 - 20℃; for 2.16667h;	98%

4-((3-chloro-4-fluorophenyl)amino)-6-nitro-7-chloroquinazoline (179552-73-9) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline

Conditions	Yield
Stage #1: (S)-3-hydroxytetyrahydrofurane With potassium tert-butylate In N,N-dimethyl-formamide at 0℃; for 2h; Stage #2: 7-chloro-N-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine With sodium benzenesulfonate In N,N-dimethyl-formamide at 30 - 90℃; for 6h;	97.8%
With potassium tert-butylate; sodium methansulfinate In N,N-dimethyl-formamide at 80℃; for 3h; Reagent/catalyst; Solvent; Temperature;	93%

2-(chloromethyl)-4-hydroxy-5,8-dihydropyridine[3,4-d]pyrimidine-7(6H)-carboxylic acid tert-butyl ester + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → 3(S)-4-hydroxy-2-(((tetrahydrofuran-3-yl)oxy)methyl)-5,8-dihydropyridin[3,4-d]pyrimidine-7(6H)-carboxylic acid tert butyl ester

Conditions	Yield
Stage #1: (S)-3-hydroxytetyrahydrofurane With sodium hydride In N,N-dimethyl-formamide for 0.5h; Stage #2: 2-(chloromethyl)-4-hydroxy-5,8-dihydropyridine[3,4-d]pyrimidine-7(6H)-carboxylic acid tert-butyl ester In N,N-dimethyl-formamide at 20℃; for 1h;	97%

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + methanesulfonyl chloride (124-63-0) → [(3S)-tetrahydrofuran-3-yl] methanesulfonate (347885-35-2)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	96%
With triethylamine In dichloromethane at 20℃; Cooling with ice;	83%
With triethylamine In dichloromethane at 0℃; for 4h;	80%

methyl 6-(2,6-difluoro-4-hydroxyphenyl)-5-fluoropyridine-2-carboxylate (1355011-30-1) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → methyl 6-{2,6-difluoro-4-[(3R)-tetrahydrofuran-3-yloxy]phenyl}-5-fluoropyridine-2-carboxylate (1395992-69-4)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃;	96%
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 2h;	96%

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + toluene-4-sulfonic acid (104-15-4) → toluene-4-sulfonic acid (S)-(tetrahydrofuran-3-yl)ester (112052-11-6)

Conditions	Yield
Stage #1: (S)-3-hydroxytetyrahydrofurane With dmap; triethylamine In dichloromethane at 0℃; for 0.166667h; Stage #2: toluene-4-sulfonic acid at 20 - 50℃; for 1.66667h;	96%

4-hydroxybenzyl chloride (35421-08-0) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (3S)-3-[p-(chloromethyl)phenoxy]tetrahydrofuran

Conditions	Yield
Stage #1: 4-hydroxybenzyl chloride In dichloromethane at -5 - 0℃; for 3h; Stage #2: (S)-3-hydroxytetyrahydrofurane With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 4.5h; Reagent/catalyst; Reflux;	95.3%

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + 4-Fluoronitrobenzene (350-46-9) → (S)-3-(4-nitrophenoxy)tetrahydrofuran

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20 - 25℃; for 1h; Inert atmosphere;	95%

C12H11Cl3N2O + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → C16H18Cl2N2O3

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃;	94.3%

fluorobenzene (462-06-6) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (S)-3-phenoxytetrahydrofuran

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran; tert-butyl alcohol at 0 - 10℃; for 1.5h; Inert atmosphere; Large scale;	94%
With potassium tert-butylate In tetrahydrofuran at 0 - 10℃; for 1h; Inert atmosphere; Large scale;	94%

(2-chloro-5-bromophenyl)(4-fluorophenyl)methanone (915095-85-1) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (S)-(5-bromo-2-chlorophenyl)(4-((tetrahydrofuran-3-yl)oxy)phenyl)methanone (915095-84-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100 - 110℃;	93%
With potassium tert-butylate In tetrahydrofuran at 7 - 10℃; for 0.5h;	87%
With potassium tert-butylate In tetrahydrofuran at 0 - 10℃; for 2h;	85.3%

6-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylquinazolin-8-ol + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (S)-6-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methyl-8-((tetrahydrofuran-3-yl)oxy)quinazoline

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; Mitsunobu Displacement; Inert atmosphere;	93%

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + 1-bromo-3-(bromomethyl)-2-fluorobenzene (149947-16-0) → (S)-3-((3-bromo-2-fluorobenzyl)oxy)tetrahydrofuran

Conditions	Yield
Stage #1: (S)-3-hydroxytetyrahydrofurane With sodium hydride In N,N-dimethyl-formamide for 1h; Inert atmosphere; Stage #2: 1-bromo-3-(bromomethyl)-2-fluorobenzene In N,N-dimethyl-formamide for 17h; Inert atmosphere;	92.51%

C20H18ClF2N5O + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline

Conditions	Yield
With potassium tert-butylate In methanol; tert-butyl alcohol at 50℃; for 1h; Solvent;	92.5%
With potassium tert-butylate In tert-butyl alcohol at 50℃; for 1h; Reagent/catalyst; Solvent;	89%
With potassium tert-butylate In tert-butyl alcohol at 50℃; for 1h; Solvent; Reagent/catalyst;	89%

(2-chloro-5-iodophenyl)(4-fluorophenyl)methanone (915095-86-2) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (S)-(2-chloro-5-iodophenyl)(4-((tetrahydrofuran-3-yl)oxy)phenyl)methanone (915095-87-3)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 16 - 25℃; for 3h;	91.8%
Stage #1: (2-chloro-5-iodophenyl)(4-fluorophenyl)methanone; (S)-3-hydroxytetyrahydrofurane With potassium tert-butylate In tetrahydrofuran at 16 - 25℃; for 4h; Stage #2: With water at 20 - 21℃; for 1.83333h;	91.8%
With potassium tert-butylate In tetrahydrofuran at 16 - 25℃; for 4h; Industry scale;	91.8%

p-fluorotoluene (352-32-9) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (S)-3-p-cresyltetrahydrofuran

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 0 - 10℃; for 1.5h; Inert atmosphere; Large scale;	91%

(S)-3-hydroxytetyrahydrofurane (86087-23-2) + methyl iodide (74-88-4) → (S)-(+)-3-methoxytetrahydrofuran

Conditions	Yield
With sodium hydride In diethyl ether at 25℃; for 24h; Etherification;	90%

6-(2,4-dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole (1618663-21-0) + (S)-3-hydroxytetyrahydrofurane (86087-23-2) → (S)-6-(2-chloro-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole (1618663-42-5)

Conditions	Yield
With sodium t-butanolate In 1,4-dioxane at 75℃; for 5h;	90%
With sodium t-butanolate In 1,4-dioxane at 25℃; for 16h;	68%

Upstream product

• 42890-76-6 (S)-1,2,4-butanetriol 
• 145873-44-5 4-chloro-3-hydroxy-1-butanol 
• 453-20-3 3-Hydroxytetrahydrofuran 
• 86087-24-3 (R)-3-Hydroxytetrahydrofuran 
• 22929-52-8 tetrahydrofuran-3-one 
• 27999-96-8 (+/-)-tetrahydrofuran-3-yl acetate 
• 115914-74-4 2-(oxiran-2-yl)ethyl 4-methylbenzenesulfonate 
• 778-29-0 but-3-enyl 4-methylbenzenesulfonate 
• 108-05-4 vinyl acetate 
• 139013-68-6 (3S)-4-chloro-1,3-butanediol 
• 167971-73-5 (2S)-2-tert-Butoxy-1,4-butanediol 
• 1708-29-8 2,5-dihydrofuran 
• 1191-99-7 2,3-dihydro-2H-furan 

Downstream Products

• 180968-44-9 [(1S,2R)-1-Benzyl-2-hydroxy-2-((13S,16R)-13-isopropyl-12,15-dioxo-2,5,8-trioxa-11,14,17-triaza-bicyclo[17.2.2]tricosa-1⁽²²⁾,19⁽²³⁾,20-trien-16-yl)-ethyl]-carbamic acid (S)-(tetrahydro-furan-3-yl) ester 
• 447402-86-0 (S)-(tetrahydro-furan-3-yl) N-(3-[isobutyl-[4-nitro-phenylsulfonyl]-amino]-2-oxo-propyl)-carbamate 
• 112052-11-6 toluene-4-sulfonic acid (S)-(tetrahydrofuran-3-yl)ester 
• 216699-85-3 Phenyl-[6-(tetrahydrofuran-3-(R)-yl-oxy)quinoxalin-2-yl]amine 
• 891842-75-4 2-(2-((4-cyanophenylamino)(5-ethoxy-2-fluoro-3-((S)-tetrahydrofuran-3-yloxy)phenyl)methyl)-1-trityl-1H-imindazol-4-yl)benzamide 
• 1147349-60-7 2-(2-((4-cyanophenylamino)(5-ethyl-2-fluoro-3-((S)-tetrahydrofuran-3-yloxy)phenyl)methyl)-1-trityl-1H-imidazol-4-yl)benzamide 
• 314771-88-5 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline 
• 1202402-49-0 (S)-2-(tetrahydrofuran-3-yloxymethyl)pyridine 
• 1358604-10-0 (S)-tetrahydrofuran-3-yl 4-nitrobenzoate 
• 1311255-48-7 (S)-4-(tetrahydrofuran-3-yloxy)-3-(trifluoromethyl)benzonitrile 
• 1395992-69-4 methyl 6-{2,6-difluoro-4-[(3R)-tetrahydrofuran-3-yloxy]phenyl}-5-fluoropyridine-2-carboxylate 
• 1393724-02-1 3-((S)-2-((4,5-dimethoxy-2-nitrobenzyloxy)carbonylamino)-3-(4-((S)-tetrahydrofuran-3-yloxy)-phenyl)propanamido)propanoic acid 

Relevant articles and documents

A S - (+) -3 - hydroxy tetrahydrofuran chemical synthesis method

The invention discloses a S - (+) - 3 - hydroxy tetrahydrofuran chemical synthesis method, includes the following operation steps: 1, compound 1 in the presence of thionyl chloride and methanol reaction to obtain compound 2; 2, in the solvent, compound 2 in the presence of a reducing agent and the reaction to obtain compound 3; 3, compound 3 in the presence of paratoluene sulfonic acid, reaction to obtain compound S - (+) - 3 - hydroxy tetrahydrofuran.

Preparation method of (S)-3-hydroxytetrahydrofuran

The invention discloses a preparation method of (S)-3-hydroxytetrahydrofuran. The problems that butantriol is difficult to separate in the production process, the yield is not high and the impurity content and the isomer content of the products are high are mainly solved. The preparation method of (S)-3-hydroxytetrahydrofuran comprises the following steps: under the existence of sulfoxide chloride, malic acid reacts with methanol to generate a compound II; under the existence of silver oxide, performing reaction on the compound II and benzyl bromide to generate a compound III; reducing the compound III by sodium borohydride to generate a compound IV; performing dehydration and ring closing on the compound IV by p-toluenesulfonic acid to generate a compound V; and taking palladium carbon asa catalyst and performing hydrogen reduction treatment on the compound V to obtain the product. The method is simple in aftertreatment and environment-friendly; the yield of the products is increasedby 80 percent or more, the purity is more than 99.5 percent and the chiral purity is more than 99.2 percent; and the method is suitable for industrialized production. (The formulas are as shown in the description).

Production technology of 3-hydroxytetrahydrofuran with high optical purity

The invention discloses a production technology of3-hydroxytetrahydrofuran with high optical purity. The production technology comprises the following steps: (1) taking chloroacetoacetic acid ethyl ester as a starting raw material, adding appropriate amount of solvents, chiral catalysts and reducing agents, and reacting at an appropriate temperature to obtain chiral ethyl 4-chloro-3-hydroxybutyrate; (2) taking the chiral ethyl 4-chloro-3-hydroxybutyrate obtained in step (1) as a raw material, adding the appropriate amount of solvents and metal borohydride reducing agents, and reacting at the appropriate temperature to obtain chiral 4-chloro-3-hydroxy-1-butanol; (3) taking the chiral 4-chloro-3-hydroxy-1-butanol obtained in step (2) as the raw material, adding appropriate amount of catalysts and solvents, and reacting at the appropriate temperature to obtain chiral 3-hydroxytetrahydrofuran. According to the production technology of the 3-hydroxytetrahydrofuran with the high optical purity, the chiral 3-hydroxytetrahydrofuran can be produced through a three-step reaction, the shortcomings of complicated production operation and high production cost are solved, and products with high optical purity can be produced.