879551-04-9

Basic information

• Product Name: (3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyl-dihydrofuran-2(3H)-one
• Synonyms: (3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyl-dihydrofuran-2(3H)-one;(3R,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyloxolan-2-one;(2R)-2-Deoxy-2-fluoro-2-methyl-D-erythro-pentonic acid gamma-lactone;(3R,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-2-one;D-erythro-Pentonic acid, 2-deoxy-2-fluoro-2-methyl-, |-lactone;D-erythro-Pentonic acid, 2-deoxy-2-fluoro-2-methyl-, gamma-lactone;-3-Fluoro-4-hydroxy-5-(hydroxymethyl);-3-methyldihydrofuran-2(3H)
• CAS NO: 879551-04-9
• Molecular Formula: C₆H₉FO₄
• Molecular Weight: 164.1316632
• Product Categories: Sofosbuvir intermediate
• Mol File: 879551-04-9.mol

Chemical Properties

• Melting Point: 142-143℃ (ethyl acetate heptane )
• Boiling Point: 352.7±42.0 °C(Predicted)
• Appearance: /
• Density: 1.42±0.1 g/cm3 (20 oC 760 Torr), Calc.*
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 11.46±0.60(Predicted)
• CAS DataBase Reference: (3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyl-dihydrofuran-2(3H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyl-dihydrofuran-2(3H)-one(879551-04-9)
• EPA Substance Registry System: (3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyl-dihydrofuran-2(3H)-one(879551-04-9)

Safety Data

• Hazardous Substances Data: 879551-04-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyl-dihydrofuran-2(3H)-one is used as a key intermediate in the asymmetric synthesis of complex organic molecules, particularly for the preparation of dibenzoyl fluoro methyl-D-ribono-γ-lactone. (3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyl-dihydrofuran-2(3H)-one is synthesized via asymmetric aldol condensation and enzymic hydrolysis from isopropylidene-D-glyceraldehyde and Et fluoropropionate, showcasing its importance in the development of novel pharmaceutical agents and advanced drug delivery systems.

Synthetic route

(2R,3R,4R)-2-fluoro-4,5-O-isopropylidene-2-methyl-3-sulfooxy-3,4,5-thydroxypentanoic acid ethyl ester tetrabutylammoniun salt → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With trifluoroacetic acid In water; acetonitrile at 80℃; for 1.5h;	100%

(S)-3-((2R,3R)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-fluoro-3-hydroxy-2-methylpropanoyl)-4-isopropyl-5,5-diphenyloxazolidin-2-one → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With lithium hydroxide monohydrate; dihydrogen peroxide In tetrahydrofuran; water at 0 - 5℃; for 1h;	100%

((2R,3R,4R)-3-benzoyloxy-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate (874638-80-9) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With methanesulfonic acid In ethanol for 5h; Reagent/catalyst; Solvent; Reflux;	95.3%
With sodium methylate In methanol at 20℃; for 2h;

(4S,5R)-ethyl-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-meth-yl-1,3,2-dioxathiolane-4-carboxylate 2,2-dioxide (879551-01-6) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Stage #1: (4S,5R)-ethyl-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-meth-yl-1,3,2-dioxathiolane-4-carboxylate 2,2-dioxide With triethylamine tris(hydrogen fluoride) In dichloromethane at 90℃; for 3h; Stage #2: With hydrogenchloride; barium(II) chloride In dichloromethane at 50℃; for 5h; Solvent; Temperature; Concentration;	89%
Multi-step reaction with 2 steps 1.1: tetraethylammonium fluoride / 1,4-dioxane / 16 h / 120 °C 1.2: 3 h / 20 °C 2.1: water; hydrogenchloride / ethanol / 48 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: triethylamine tris(hydrogen fluoride) / 2 h / 82 - 85 °C 2.1: hydrogenchloride / 0.5 h / 90 - 92 °C 2.2: 4 h View Scheme

C11H19FO5 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With hydrogenchloride In ethanol; water at 50℃; for 24h; Reagent/catalyst; Solvent; Temperature; Concentration;	88%

2-deoxy-2-fluoro-3,4-O-isopropylidene-2-C-methyI-D-ribono-1,5-lactone → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + 2-deoxy-2-fluoro-2-C-methyI-D-ribono-1,5-lactone

Conditions	Yield
With trifluoroacetic acid In 1,4-dioxane; water at 20℃; for 48h;	A 83% B 6%

(S)-3-((2R,3R)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-fluoro-3-hydroxy-2-methylpropanoyl)-4-benzyloxazolidin-2-one (1616508-45-2) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With lithium hydroxide monohydrate; dihydrogen peroxide In tetrahydrofuran; water at 0 - 5℃; for 1h;	70%

(S)-3-((2R,3R)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-fluoro-3-hydroxy-2-methylpropanoyl)-4-isopropyloxazolidin-2-one (1616508-57-6) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With lithium hydroxide monohydrate; dihydrogen peroxide In tetrahydrofuran; water at 0 - 5℃; for 1h;	67%

((2S,3R,4R)-4-fluoro-3-hydroxy-4-methyl-5-oxotetrahydrofuran-2-yl)methyl methanesulfonate → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With water; potassium hydroxide In ethanol for 4h; Reflux;	45%

C6H15N*C11H19FO8S → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Stage #1: C6H15N*C11H19FO8S With hydrogenchloride; water at 90℃; for 0.5h; Stage #2: With barium(II) chloride In water at 90℃; for 4h;
Stage #1: C6H15N*C11H19FO8S With hydrogenchloride at 90 - 92℃; for 0.5h; Stage #2: With barium(II) chloride In water for 4h; Temperature;

C13H22FNO4 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (1040882-61-8)

Conditions	Yield
With water; acetic acid at 95℃; for 2 - 5h; Product distribution / selectivity;

C15H19FO4S → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (1040882-61-8)

Conditions	Yield
With water; acetic acid at 95℃; for 2 - 5h; Product distribution / selectivity;

C16H18FNO6 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (1040882-61-8)

Conditions	Yield
With water; acetic acid at 95℃; for 2 - 5h; Product distribution / selectivity;

C15H19FO4S → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (1040882-61-8)

Conditions	Yield
With water; acetic acid at 90℃; for 2h; optical yield given as %de;

C16H18FNO6 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (1040882-61-8)

Conditions	Yield
With water; acetic acid at 90℃; for 2h; optical yield given as %de;

C11H19FO5 (1033394-83-0) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With hydrogenchloride In ethanol; water at 20℃; for 15h;
With hydrogenchloride; water In ethanol at 20℃; for 21h;

(2S,3R)-3-[(4R)-2,2-dimethyl-[1,3]dioxolane-4-yl]-2,3-dihydroxy-2-methylpropionic acid ethyl ester (93635-76-8) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: fluorosulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine tris(hydrogen fluoride) / acetonitrile / 5 h / -15 - 90 °C 2: 2,2-dimethoxy-propane; hydrogenchloride; water / tetrahydrofuran / 3 h / 20 °C 3: hydrogenchloride; water / ethanol / 21 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine; sulfuryl dichloride / dichloromethane / 2 h / 0 - 20 °C 2.1: tetraethylammonium fluoride / 1,4-dioxane / 16 h / 120 °C 2.2: 3 h / 20 °C 3.1: water; hydrogenchloride / ethanol / 48 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: Isopropyl acetate; triethylamine; thionyl chloride / acetonitrile / 1 h / 6 - 9 °C 1.2: 0.5 h 2.1: triethylamine tris(hydrogen fluoride) / 2 h / 82 - 85 °C 3.1: hydrogenchloride / 0.5 h / 90 - 92 °C 3.2: 4 h View Scheme

C10H18O6 (1351925-17-1) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: fluorosulfonyl fluoride; triethylamine; 1,8-diazabicyclo[5.4.0]undec-7-ene hydrofluoride / acetonitrile / 5 h / 0 - 55 °C 2: 2,2-dimethoxy-propane; water; sulfuric acid / 1,4-dioxane / 16 h / 20 °C / pH 2 - 3 / Cooling with ice 3: hydrogenchloride; water / ethanol / 18 h / 20 °C View Scheme

C10H16FO8S(1-) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2,2-dimethoxy-propane; water; sulfuric acid / 1,4-dioxane / 16 h / 20 °C / pH 2 - 3 / Cooling with ice 2: hydrogenchloride; water / ethanol / 18 h / 20 °C View Scheme

C10H17FO5 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With hydrogenchloride; water In ethanol at 20℃; for 18h; Solvent;

C11H18O4 (130606-67-6) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium permanganate / acetone / 5 h / 0 - 5 °C 2.1: triethylamine; sulfuryl dichloride / dichloromethane / 2 h / 0 - 20 °C 3.1: tetraethylammonium fluoride / 1,4-dioxane / 16 h / 120 °C 3.2: 3 h / 20 °C 4.1: water; hydrogenchloride / ethanol / 48 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium hydrogencarbonate; sodium permanganate; ethylene glycol / acetone / 1.5 h / -15 - 10 °C 2.1: Isopropyl acetate; triethylamine; thionyl chloride / acetonitrile / 1 h / 6 - 9 °C 2.2: 0.5 h 3.1: triethylamine tris(hydrogen fluoride) / 2 h / 82 - 85 °C 4.1: hydrogenchloride / 0.5 h / 90 - 92 °C 4.2: 4 h View Scheme

C12H21FO4 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With hydrogenchloride; water In ethanol at 20℃; for 48h;	110 g

ethyl 2-fluoropropionate (349-43-9) + 2,3-isopropylidene-glyceraldehyde (15186-48-8) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (1040882-61-8)

Conditions	Yield
Stage #1: ethyl 2-fluoropropionate; 2,3-isopropylidene-glyceraldehyde With lithium diisopropyl amide In tetrahydrofuran at -70 - 20℃; for 2h; Stage #2: With acetic acid In water at 90℃; for 2h;

C18H22FNO6 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
With hydrogenchloride In ethanol; water for 4h; Reflux;

(S,E)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-methylpropionic acid ethyl ester (81997-76-4) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate; dihydrogen peroxide / ethanol; benzonitrile / 0 °C 2: triethylamine; triethylamine tris(hydrogen fluoride) / 80 °C / Inert atmosphere 3: hydrogenchloride / ethanol; water / 24 h / 50 °C View Scheme

C11H18O5 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; triethylamine tris(hydrogen fluoride) / 80 °C / Inert atmosphere 2: hydrogenchloride / ethanol; water / 24 h / 50 °C View Scheme

C10H17FO5 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (1040882-61-8) + C6H9FO4 + C6H9FO4

Conditions	Yield
With acetic acid In water at 90℃; for 1h; Overall yield = 28.9 g;

C14H24FNO4 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + (3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (1040882-61-8) + C6H9FO4 + C6H9FO4

Conditions	Yield
With acetic acid In water at 90℃; for 1h; Overall yield = 8.72 g;

ethyl (E)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-methyl-2-propenoate (127642-52-8) → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium permanganate; ethylene glycol; sodium hydrogencarbonate / water; ethyl acetate / -10 - 0 °C / Large scale 2: triethylamine; sulfuryl dichloride / ethyl acetate / 5 - 25 °C / Large scale 3: potassium fluoride / ethyl acetate / 5 h / Reflux; Large scale 4: hydrogenchloride / water; ethyl acetate / 2 h / 85 - 90 °C / Large scale View Scheme

C11H20O6 → (3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine; sulfuryl dichloride / ethyl acetate / 5 - 25 °C / Large scale 2: potassium fluoride / ethyl acetate / 5 h / Reflux; Large scale 3: hydrogenchloride / water; ethyl acetate / 2 h / 85 - 90 °C / Large scale View Scheme

(3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) → (3R,4R,5R)-3-fluoro-5-(hydroxymethyl)-3-methyltetrahydrofuran-2,4-diol

Conditions	Yield
With lithium borohydride In tetrahydrofuran at 0℃; for 6h; Solvent; Concentration; Inert atmosphere;	94%
With lithium tri-t-butoxyaluminum hydride In tetrahydrofuran at -20 - 0℃; for 0.5h; Reagent/catalyst;

(3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + tert-butyldimethylsilyl chloride (18162-48-6) → C12H23FO4Si

Conditions	Yield
With pyridine; 1H-imidazole at 0 - 20℃; for 16h;	88%
With pyridine; 1H-imidazole In dichloromethane at 20℃; Cooling with ice;	63%
With pyridine; 1H-imidazole In dichloromethane at 20℃; Cooling with ice;	57.3%

(3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) + benzoyl chloride (98-88-4) → ((2R,3R,4R)-3-benzoyloxy-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate (874638-80-9)

Conditions	Yield
With pyridine at 20℃; for 0.333333h;	87%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 12h;	86%
With dmap; triethylamine In acetonitrile at 5 - 20℃; for 2h; Temperature;	84.2%

(3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) → ((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-5-hydroxy-4-methyltetrahydrofuran-2-yl)methyl benzoate

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 0.75 h / 0 - 20 °C 2: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 1 h / -78 - -20 °C / Inert atmosphere View Scheme

(3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) → (((2R,3R,4R,5R)-3-(benzoyloxy)-5-bromo-4-fluoro-4-methyltetrahydrofuran-2-yl)methyl benzoate) (1199809-24-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / 0.75 h / 0 - 20 °C 2: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 1 h / -78 - -20 °C / Inert atmosphere 3: carbon tetrabromide; triphenylphosphine / dichloromethane / 0.33 h / -25 - -20 °C / Inert atmosphere View Scheme

(3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) → (2R,3R,4R,5R)-5-(2-amino-6-chloro-9H-purin-9-yl)-2-((benzoyloxy)methyl)-4-fluoro-4-methyltetrahydrofuran-3-yl benzoate (1199809-26-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: pyridine / 0.75 h / 0 - 20 °C 2.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 1 h / -78 - -20 °C / Inert atmosphere 3.1: carbon tetrabromide; triphenylphosphine / dichloromethane / 0.33 h / -25 - -20 °C / Inert atmosphere 4.1: potassium tert-butylate / acetonitrile; tert-butyl alcohol / 0.5 h / 35 °C 4.2: 50 °C View Scheme

(3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) → C31H30FN5O5 (1613589-61-9)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: pyridine / 0.75 h / 0 - 20 °C 2.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 1 h / -78 - -20 °C / Inert atmosphere 3.1: carbon tetrabromide; triphenylphosphine / dichloromethane / 0.33 h / -25 - -20 °C / Inert atmosphere 4.1: potassium tert-butylate / acetonitrile; tert-butyl alcohol / 0.5 h / 35 °C 4.2: 50 °C 5.1: silver nitrate / dichloromethane / 20 °C 5.2: 12 h / 20 °C View Scheme

(3R,4R,5R)-3‑fluoro‑4‑hydroxy‑5‑(hydroxymethyl)‑3‑methyltetrahydrofuran‑2‑one (879551-04-9) → C31H29FIN5O4 (1613589-62-0)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: pyridine / 0.75 h / 0 - 20 °C 2.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 1 h / -78 - -20 °C / Inert atmosphere 3.1: carbon tetrabromide; triphenylphosphine / dichloromethane / 0.33 h / -25 - -20 °C / Inert atmosphere 4.1: potassium tert-butylate / acetonitrile; tert-butyl alcohol / 0.5 h / 35 °C 4.2: 50 °C 5.1: silver nitrate / dichloromethane / 20 °C 5.2: 12 h / 20 °C 6.1: triphenylphosphine; pyridine; iodine / 20 °C View Scheme

Upstream product

• 1946820-88-7 C₁₁H₂₀O₆ 
• 127642-52-8 ethyl (E)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-methyl-2-propenoate 
• 81997-76-4 (S,E)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-methylpropionic acid ethyl ester 
• 874638-80-9 ((2R,3R,4R)-3-benzoyloxy-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate 
• 349-43-9 ethyl 2-fluoropropionate 
• 15186-48-8 2,3-isopropylidene-glyceraldehyde 
• 879551-01-6 (4S,5R)-ethyl-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-meth-yl-1,3,2-dioxathiolane-4-carboxylate 2,2-dioxide 
• 130606-67-6 C₁₁H₁₈O₄ 
• 1616508-57-6 (S)-3-((2R,3R)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-fluoro-3-hydroxy-2-methylpropanoyl)-4-isopropyloxazolidin-2-one 
• 1616508-45-2 (S)-3-((2R,3R)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-fluoro-3-hydroxy-2-methylpropanoyl)-4-benzyloxazolidin-2-one 

Downstream Products

• 1199809-24-9 (((2R,3R,4R,5R)-3-(benzoyloxy)-5-bromo-4-fluoro-4-methyltetrahydrofuran-2-yl)methyl benzoate) 
• 1199809-26-1 (2R,3R,4R,5R)-5-(2-amino-6-chloro-9H-purin-9-yl)-2-((benzoyloxy)methyl)-4-fluoro-4-methyltetrahydrofuran-3-yl benzoate 
• 1613589-61-9 C₃₁H₃₀FN₅O₅ 
• 1613589-62-0 C₃₁H₂₉FIN₅O₄ 
• 1613589-63-1 C₃₁H₂₈FN₅O₄ 
• 1613589-64-2 C₃₁H₂₈F₂IN₅O₄ 
• 1613589-65-3 C₃₈H₃₂F₂IN₅O₅ 
• 1613589-66-4 C₄₅H₃₇F₂N₅O₇ 
• 1613589-67-5 C₃₁H₂₉F₂N₅O₅ 
• 1613589-69-7 9-(2-deoxy-2-fluoro-2-C-methyl-β-D-ribofuranosyl)-6-ethoxy-2-((4-monomethoxytrityl)amino)purine 
• 1613589-70-0 9-(2,5-dideoxy-2-fluoro-2-C-methyl-5-iodo-β-D-ribofuranosyl)-6-ethoxy-2-((4-monomethoxytrityl)amino)purine 
• 1613589-71-1 9-(4,5-didehydro-2,5-dideoxy-2-fluoro-2-C-methyl-β-D-ribofuranosyl)-6-ethoxy-2-((4-monomethoxytrityl)amino)purine 
• 1613589-72-2 9-(2,5-dideoxy-2,4-difluoro-5-iodo-2-C-methyl-β-D-ribofuranosyl)-6-ethoxy-2-((4-monomethoxytrityl)amino)purine 
• 1613589-73-3 C₄₀H₃₆F₂IN₅O₅ 

Relevant articles and documents

BI- AND MONOCYCLIC NUCLEOSIDE ANALOGS FOR TREATMENT OF HEPATITIS E

The present disclosure is directed toward bi- and monocyclic nucleoside analogs, and compositions comprising these compounds for use in the treatment of hepatitis E infections.

Method for preparing 3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-one

The invention discloses a method for preparing 3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-one, comprising the following steps that: ((2R, 3R, 4R)-3-(benzyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl) methyl benzoate is dispersed in an organic solvent, excessive strong acid is added for heating reflux, the organic solvent is removed, and pulping, filtering and drying are performed, wherein the strong acid is methanesulfonic acid, sulfuric acid, trifluoromethanesulfonic acid or concentrated hydrochloric acid. ((2R, 3R, 4R)-3-(benzyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl) methyl benzoate is adopted as a raw material to be subjected to a reflux reaction with excessive specific strong acid, a high-purity and high-yield product can be obtained only through a one-step reaction, the process steps are simple, and mass production of the product is facilitated.

PROCESS FOR PREPARATION OF LACTONE DERIVATIVES AND INTERMEDIATES THEREOF

A novel process for the preparation of lactone derivatives, and intermediates thereof is described. The lactone derivatives are important precursors for the synthesis of anti-hepatitis C virus agents, including sofosbuvir.

Preparation method of sofosbuvir intermediate

The invention discloses a preparation method of a sofosbuvir intermediate of (2R)-2-deoxy-2-fluoro-2-methyl-D-erythro-pentonic acid-g-lactone 3,5-dibenzoate. The intermediate structure corresponds toa formula I shown as the description. The method comprises the step that the sofosbuvir intermediate shown as the formula I is finally obtained by using (D2) (S)-(+)-4-phenyl-2-oxazolidinone of a compound shown as a formula II as a raw material through six-step reaction of condensation, fluorination, Adol addition, oxidation cyclization, isomerization and benzoylation. The preparation method hasthe advantages that the raw materials are cheap and can be easily obtained; the reaction conditions are mild; the route is short; the yield is high; three wastes are few; the pollution is little; thepreparation method is suitable for industrial production.

Synthesizing method for drug intermediate

The invention discloses a synthesizing method for a drug intermediate, and relates to the field of drug synthesis, in particular to the field of organic synthesis. In the synthesizing method, compound V(4S,5R)-ethyl-5-((R)-2,2-dimethyl-1,3-dioxolame-4-base)-4-methyl-1,3,2-dioxathiolane-4- carboxylic acid-2,2'dioxide serves as a raw material, a compound II is prepared through three synthesizing methods, and an intermediate compound I is prepared through the compound II. The provided synthesizing technology has the beneficial effects that cost is low, few byproducts are generated, the yield is high, and pollution to the environment is weak.

Preparation method for 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone

The invention discloses a preparation method for 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone. The preparation method comprises the following steps: subjecting a starting raw material D-mannitol to acetone protection and sodium periodate oxidation; then subjecting the treated D-mannitol and a self-made ylide reagent to the Witting reaction; then carrying out selective oxidation by using an aqueous sodium permanganate solution; then successively carrying out sulfonylation, fluorination with potassium fluoride, and ring closing with a concentrated protective group protective group; protecting the hydroxyl group by using benzoyl chloride; and then carrying out purification so as to obtain the final product 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone. The preparation method provided by the invention uses easily available and cheap raw materials, so production cost is greatly reduced; and the operation of the preparation method is coherent and simple, and the quantity of waste gas, waste water and industrial residues is lower than the quantity of waste gas, waste water and industrial residues reported in the prior art.

Preparation for sofosbuvir key intermediate

The invention relates to preparation for a sofosbuvir key intermediate. With (E)-(S)-3-(2,2-dimethyl-1,3-dioxolane-4-base)-2-ethyl methacrylate being an initial raw material, preparation of 3,5-bis-O-benzoyl-2-deoxidation-2-fluorine-2-C-methyl-D-riboic acid-gamma-lactone is achieved through an epoxidation reaction, fluoridation, a de-acetonylidene cyclization reaction and a benzoyl reaction. According to the method, a synthesis route is short, and in the reaction process, a reagent that oxidability is high, and in the aftertreatment process, potassium permanganate or sodium permanganate and high-corrosivity SOCl2 deep in waste water color will generate a lot of waste water will not be involved.

Method for preparing intermediate of Sofosbuvir

The invention provides a method for preparing 3,5-bis-O-benzoyl-2-deoxy-2-fluoro-2-C-methyl-D-ribose-gamma-lactone of D-ribofuranose lactone (structural formula 1). The compound is an important intermediate of a hepatitis C virus (HCV) NS5B polymerase inhibitor Sofosbuvir. The formula 1 is shown in the specification.

PRODUCTION METHOD OF (2R)-2-FLUORO-2-C-METHYL-D-RIBONO-γ-LACTONE

PROBLEM TO BE SOLVED: To provide a production method of (2R)-2-fluoro-2-C-methyl-D-ribono-γ-lactone. SOLUTION: A (2R)-2-fluoro-2-C-methyl-D-ribono-γ-lactone precursor containing various diastereomers can be produced by performing Reformatsky reaction using activated metal to a 2-fluoro-2-halopropionate derivative and a D-glyceraldehyde derivative. The obtained mixture containing the (2R)-2-fluoro-2-C-methyl-D-ribono-γ-lactone precursor is subjected to deprotection and lactonizing under an acidic condition, is converted to a diastereomer mixture containing 2-fluoro-2-C-methyl-D-ribono-γ-lactone and is recrystallized, thereby inducing the mixture to (2R)-2-fluoro-2-C-methyl-D-ribono-γ-lactone. COPYRIGHT: (C)2015,JPOandINPIT

The synthesis of hydroxyaminopurine nucleosied (by machine translation)

A compound or salt thereof having the following structure useful for the treatment of hepatitis C virus (HCV): wherein R 7 is C 1-6 alkyl or C 3-6 cycloalkyl and R 8 is -O(C 1-6 alkyl) or -O(C 3-6 cycloalkyl).