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
• Article Data: 20

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

(3R,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one can be used for synthetic preparation for asymmetric synthesis of dibenzoyl fluoro methyl-D-ribono-γ-lactone via asymmetric aldol condensation and enzymic hydrolysis from isopropylidene-D-glyceraldehyde and Et fluoropropionate.

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

• 1033394-83-0 C₁₁H₁₉FO₅ 
• 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 

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.

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.

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.