122111-01-7

Basic information

• Product Name: 2-Deoxy-2,2-difluoro-D-erythro-pentafuranous-1-ulose-3,5-dibenzoate
• Synonyms: 2-deoxy-2,2-difluor opentofuranos-1-ulose-3,5-dibenzoate;2-Doexy-2,2-difluoro-D-Erythro-pentofuranous-1-ulose-3,5-dibenzoate;GEMCITABINE INTERMEDIATE;2-Deoxy-2,2-difluoro-D-erythro-pentafuranous-1-ulose-3,5-dibenzoate;2-DEOXY-2,2-DIFLUORO-D-ERYTHRO-PENTOFURANOS-1-ULOSE-3,5-DIBENZOATE:95+%;2-deoxy-2,2-difluoro-D-erythro- pentofuranos-1-ulose-3,5-dibenzoate(T6);3, 5-DISBENZOYLOXY-2-DEOXY-2, 2-DIFLUORO-1-OXORIBOSE;2-Deoxy-2,2-Difluoro-D-Ribofuranofuranose-3,5 CDibenzoate
• CAS NO: 122111-01-7
• Molecular Formula: C₁₉H₁₄F₂O₆
• Molecular Weight: 376.31
• EINECS: 1592732-453-0
• Product Categories: INTERMEDIATESOFGEMCITABINE;13C & 2H Sugars;Carbohydrates & Derivatives;Antineoplastic drug, difluorine nucleoside analog
• Mol File: 122111-01-7.mol
• Article Data: 8

Chemical Properties

• Melting Point: 117-119 °C(lit.)
• Boiling Point: 437.216 °C at 760 mmHg
• Flash Point: 210.499 °C
• Appearance: off-white solid
• Density: 1.41 g/cm³
• Vapor Pressure: 7.61E-08mmHg at 25°C
• Refractive Index: 1.57
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 2-Deoxy-2,2-difluoro-D-erythro-pentafuranous-1-ulose-3,5-dibenzoate(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Deoxy-2,2-difluoro-D-erythro-pentafuranous-1-ulose-3,5-dibenzoate(122111-01-7)
• EPA Substance Registry System: 2-Deoxy-2,2-difluoro-D-erythro-pentafuranous-1-ulose-3,5-dibenzoate(122111-01-7)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 122111-01-7(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 122111-01-7 differently. You can refer to the following data:
1. 2-Deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (CAS: 122111-01-7) is a compound useful in organic synthesis and it is the key intermediate of gemcitabine.
2. 2-Deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (cas# 122111-01-7) is a compound useful in organic synthesis.

Chemical Properties

Off-White Solid

InChI:InChI=1/C19H14F2O6/c20-19(21)15(27-17(23)13-9-5-2-6-10-13)14(26-18(19)24)11-25-16(22)12-7-3-1-4-8-12/h1-10,14-15H,11H2

Synthetic route

benzoyl chloride (98-88-4) + 2-deoxy-2,2-difluoro-1-carbonylribose (95058-77-8) → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
With pyridine; dmap In dichloromethane for 1.5h; Reflux;	67%
With pyridine; dmap In ethyl acetate at 20℃; for 12h; Reflux;	58.3 g
With pyridine In dichloromethane at 0 - 20℃; for 0.666667h;
With pyridine; dmap at 30 - 50℃; for 8h; Inert atmosphere; Large scale;

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate + C19H16F2O7 (866473-33-8) → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
toluene-4-sulfonic acid In toluene Product distribution / selectivity; Heating / reflux; Dean and Stark apparatus;	34%

C5H6F2O4 + benzoyl chloride (98-88-4) + 2-deoxy-2,2-difluoro-1-carbonylribose (95058-77-8) → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate + C19H16F2O7 (866473-33-8) + 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
With pyridine; dmap In ethyl acetate at 60 - 65℃; for 6h; Product distribution / selectivity;

C19H16F2O7 → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
toluene-4-sulfonic acid In toluene Product distribution / selectivity; Heating / reflux; Dean and Stark apparatus;

pyridine (110-86-1) + benzoyl chloride (98-88-4) + 2-deoxy-2,2-difluoro-1-carbonylribose (95058-77-8) → pyridine hydrochloride (628-13-7) + 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
With dmap In ethyl acetate at 60 - 65℃; for 6.25h;

ethyl 2-deoxy-2,2-difluoro-D-erythro,D-threo-pentonate (114420-06-3) + benzoyl chloride (98-88-4) → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
Stage #1: ethyl 2-deoxy-2,2-difluoro-D-erythro,D-threo-pentonate; toluene-4-sulfonic acid In water at 75 - 80℃; for 3h; Stage #2: benzoyl chloride With pyridine; dmap In ethyl acetate at 60 - 65℃; for 3h; Product distribution / selectivity; Dean and Stark apparatus;

2-deoxy-2,2-difluoropentofuranos-1-ulose + benzoyl chloride (98-88-4) → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
With pyridine In ethyl acetate at 25 - 60℃; Inert atmosphere;

benzoyl chloride (98-88-4) + ethyl (3R,S)-2,2-difluoro-3-hydroxy-(2,2-dimethyldioxolpent-4-yl)propionate (928797-50-6) → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
Stage #1: ethyl (3R,S)-2,2-difluoro-3-hydroxy-(2,2-dimethyldioxolpent-4-yl)propionate With water; pyridinium trifluroacetate In water; acetonitrile for 3h; Heating / reflux; Stage #2: benzoyl chloride With pyridine; dmap In ethyl acetate at 0 - 65℃; for 10h; Product distribution / selectivity;
Stage #1: ethyl (3R,S)-2,2-difluoro-3-hydroxy-(2,2-dimethyldioxolpent-4-yl)propionate With water; pyridinium p-toluenesulfonate In water; acetonitrile for 12h; Heating / reflux; Stage #2: benzoyl chloride With pyridine; dmap In ethyl acetate at 0 - 65℃; for 10h; Product distribution / selectivity;

C8H8F2O5 → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetic acid / chloroform / 2 h / 50 °C 2.1: sodium tetrahydroborate / tetrahydrofuran / 0.5 h 2.2: 2 h / 25 °C 3.1: pyridine; dmap / dichloromethane / 1.5 h / Reflux View Scheme

ethyl (3R,S)-2,2-difluoro-3-hydroxy-(2,2-dimethyldioxolpent-4-yl)propionate (928797-50-6) → 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 70 - 80 °C / Large scale 2: pyridine; dmap / 8 h / 30 - 50 °C / Inert atmosphere; Large scale View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → (2R,3R)-2-((benzoyloxy)methyl)-4,4-difluoro-5-hydroxyoxolan-3-yl benzoate (1173824-58-2)

Conditions	Yield
With lithium tri-t-butoxyaluminum hydride In tetrahydrofuran; diethyl ether at 10 - 30℃; for 1h;	100%
Stage #1: 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate With sodium bis(2-methoxyethoxy)aluminium dihydride In tetrahydrofuran; toluene at -30℃; for 1h; Stage #2: With hydrogenchloride In tetrahydrofuran; water; toluene	99.5%
With lithium tri-t-butoxyaluminum hydride In tetrahydrofuran; diethyl ether at -78℃; for 1h; Inert atmosphere;	84%

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → Benzoic acid (2R,3R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-4,4-difluoro-3-hydroxy-tetrahydro-furan-2-ylmethyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / LiAl(OBu-t)3H / diethyl ether; tetrahydrofuran / 1 h / 10 - 30 °C 2: 100 percent / triethylamine / CH2Cl2 / 2 h / 23 °C 3: 1) Me3SiOTf / 1) 1,1,2-trichloroethane, r.t., 30 min, 2) 113 deg C, 18 h 4: ammonia / methanol View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 1-(2'-deoxy-2',2'-difluoro-3',5'-di-O-benzoyl-D-ribofuranosyl)-4-acetamidopyrimidin-2-one (143157-23-7, 143157-26-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 100 percent / LiAl(OBu-t)3H / diethyl ether; tetrahydrofuran / 1 h / 10 - 30 °C 2: 100 percent / triethylamine / CH2Cl2 / 2 h / 23 °C 3: 1) Me3SiOTf / 1) 1,2-dichloroethane, 30 deg C, 1 h, 2) 1,2-dichloroethane, 83 deg C, overnight View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 2’-deoxy-2’,2’-difluoro-cytidine (103882-84-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / LiAl(OBu-t)3H / diethyl ether; tetrahydrofuran / 1 h / 10 - 30 °C 2: 100 percent / triethylamine / CH2Cl2 / 2 h / 23 °C 3: 1) Me3SiOTf / 1) 1,2-dichloroethane, 30 deg C, 1 h, 2) 1,2-dichloroethane, 83 deg C, overnight 4: 1.73 kg / ammonia (gas) / methanol / Ambient temperature View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-1-O-methanesulfonyl-D-erythro-pentofuranose (134877-42-2, 134877-43-3, 122111-11-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 100 percent / LiAl(OBu-t)3H / diethyl ether; tetrahydrofuran / 1 h / 10 - 30 °C 2: 100 percent / triethylamine / CH2Cl2 / 2 h / 23 °C View Scheme
Multi-step reaction with 2 steps 1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran / 2 h / -78 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2 h / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: lithium tri-(tert-butoxy)aluminum hydride / tetrahydrofuran / 2 h / -78 - 20 °C / Inert atmosphere 2: triethylamine / tetrahydrofuran; dichloromethane / 2 h / 0 - 20 °C View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C23H19F2N3O6 (134790-40-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 100 percent / LiAl(OBu-t)3H / diethyl ether; tetrahydrofuran / 1 h / 10 - 30 °C 2: 100 percent / triethylamine / CH2Cl2 / 2 h / 23 °C 3: 1) Me3SiOTf / 1) 1,1,2-trichloroethane, r.t., 30 min, 2) 113 deg C, 18 h View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → (2'-deoxy-2',2'-difluorocytidine)-3',5'-dibenzoate (134790-39-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 100 percent / LiAl(OBu-t)3H / diethyl ether; tetrahydrofuran / 1 h / 10 - 30 °C 2: 100 percent / triethylamine / CH2Cl2 / 2 h / 23 °C 3: 1) Me3SiOTf / 1) 1,1,2-trichloroethane, r.t., 30 min, 2) 113 deg C, 18 h View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate + 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C19H16F2O7

Conditions	Yield
With hydrogenchloride In water at 45 - 50℃; for 3h;

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-D-β-ribofuranose + 3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-D-α-ribofuranose

Conditions	Yield
Stage #1: 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate With sodium bis(2-methoxyethoxy)aluminium dihydride In tetrahydrofuran; toluene at -70 - -50℃; for 1h; Stage #2: With hydrogenchloride; methanol; water In tetrahydrofuran; toluene for 0.5h;
With lithium tri-t-butoxyaluminum hydride In tetrahydrofuran; diethyl ether at 20℃; for 1.5h; Inert atmosphere; Overall yield = 99.8 %; Overall yield = 10 g;	A n/a B n/a
With sodium tetrahydroborate; zinc(II) chloride; tert-butyl alcohol In tetrahydrofuran; ethyl acetate at 15℃; Overall yield = 100 %;

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C19H15(3)HF2O6

Conditions	Yield
Stage #1: 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate With C10H22(3)HB In tetrahydrofuran at 0 - 20℃; for 17.5h; Inert atmosphere; Cooling with ice; Stage #2: With water In tetrahydrofuran for 0.5h; Inert atmosphere; Reflux;

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C19H15(2)HF2O6

Conditions	Yield
Stage #1: 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate With C10H22(2)HB In tetrahydrofuran at 0 - 20℃; for 17.5h; Inert atmosphere; Cooling with ice; Stage #2: With water In tetrahydrofuran for 0.5h; Inert atmosphere; Reflux;

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranos-1-yl)-5-chlorouracil (132786-36-8)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranos-1-yl)thymine (95058-80-3)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C25H25F2IN3O9P (1321580-98-6)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite 5.1: 1-methyl-1H-imidazole / tetrahydrofuran / 24 h / 20 °C / Inert atmosphere View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C19H21F2IN3O9P (1321581-00-3)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite 5.1: 1-methyl-1H-imidazole / tetrahydrofuran / 24 h / 20 °C / Inert atmosphere View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C29H27F2IN3O9P (1321581-01-4)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite 5.1: 1-methyl-1H-imidazole / tetrahydrofuran / 24 h / 20 °C / Inert atmosphere View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C23H23F2IN3O9P (1321581-02-5)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite 5.1: 1-methyl-1H-imidazole / tetrahydrofuran / 24 h / 20 °C / Inert atmosphere View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C25H25BrF2N3O9P (1321581-03-6)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite 5.1: 1-methyl-1H-imidazole / tetrahydrofuran / 24 h / 20 °C / Inert atmosphere View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → C25H25ClF2N3O9P (1321581-04-7)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite 5.1: 1-methyl-1H-imidazole / tetrahydrofuran / 24 h / 20 °C / Inert atmosphere View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranos-1-yl)-5-iodouracil (132832-46-3)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranos-1-yl)-5-bromouracil (132786-35-7)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C 4.1: sodium methylate / methanol / 20 °C / Inert atmosphere 4.2: Amberlite View Scheme

2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate (122111-01-7) → 1-(3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-β-D-erythro-pentofuranos-1-yl)-5-iodouracil (1321580-93-1) + 1-(3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-α-D-erythro-pentofuranos-1-yl)-5-iodouracil

Conditions	Yield
Multi-step reaction with 3 steps 1.1: lithium tri-t-butoxyaluminum hydride / tetrahydrofuran; diethyl ether / 1 h / -78 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 18 h / 0 - 20 °C / Inert atmosphere 3.1: trimethylsilyl trifluoromethanesulfonate / 1,1-dichloroethane / 10 h / 90 - 100 °C / Inert atmosphere 3.2: 20 °C View Scheme

Upstream product

• 110-86-1 pyridine 
• 98-88-4 benzoyl chloride 
• 95058-77-8 2-deoxy-2,2-difluoro-1-carbonylribose 
• 114420-06-3 ethyl 2-deoxy-2,2-difluoro-D-erythro,D-threo-pentonate 
• 928797-50-6 ethyl (3R,S)-2,2-difluoro-3-hydroxy-(2,2-dimethyldioxolpent-4-yl)propionate 
• 122111-02-8 2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-dibenzoate 
• 866473-33-8 C₁₉H₁₆F₂O₇ 

Downstream Products

• 95058-80-3 1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranos-1-yl)thymine 
• 1321580-98-6 C₂₅H₂₅F₂IN₃O₉P 
• 1321581-00-3 C₁₉H₂₁F₂IN₃O₉P 
• 1321581-01-4 C₂₉H₂₇F₂IN₃O₉P 
• 1321581-03-6 C₂₅H₂₅BrF₂N₃O₉P 
• 1321581-04-7 C₂₅H₂₅ClF₂N₃O₉P 
• 153012-08-9 C₁₉H₁₆F₂O₆ 
• 1173824-58-2 (2R,3R)-2-((benzoyloxy)methyl)-4,4-difluoro-5-hydroxyoxolan-3-yl benzoate 
• 1445381-44-1 (2R,3R,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-2-((benzoyloxy)methyl)-4,4-difluorotetrahydrofuran-3-yl benzoate 

Relevant articles and documents

High-selectivity synthesis method for gemcitabine intermediate

The invention discloses a high-selectivity synthesis method for a gemcitabine intermediate. The high-selectivity synthesis method specifically comprises the following process: Step 1, synthesis of T1;Step2, synthesis of T2, to be specific, 550kg of hydrogen peroxide is dropwise added into the T1, and a reaction is controlled to produce the T2; Step3, synthesis of T3, to be specific, sodium acetate trihydrate or sodium carbonate is added into a reaction kettle, the PH value is adjusted with glacial acetic acid, a 10%-15% sodium hypochlorite aqueous solution is dropwise added, and a reaction iscontrolled to produce the T3; Step 4, synthesis of T4; Step 5, synthesis of T5; Step 6, synthesis of T6; Step 7, synthesis of T7; Step 8, synthesis of T8; and Step9, T8 configuration transformation.The high-selectivity synthetic method for the gemcitabine intermediate can reduce the production cost, and meanwhile, can also increase the yield of the gemcitabine intermediate.

Method for preparing Gemcitabine intermediate from chiral catalyst

The invention relates to a method for preparing a Gemcitabine intermediate from a chiral catalyst, and belongs to the technical field of synthesis of medical intermediates. In order to solve the problem that the existing reaction is poor in stereoselectivity, the invention provides the method for preparing the Gemcitabine intermediate from the chiral catalyst; the method comprises the following steps: performing a condensation reaction on R-glyceraldehyde acetonide and difluoro halogenated ethyl acetate in an inert organic solvent under the combined catalytic action of active zinc powder and delta-amino alcohol ligands to obtain a corresponding intermediate; performing deprotection and lactonization treatment on the intermediate and performing a reaction on the intermediate and benzoyl chloride in the presence of an acid-binding agent to obtain the corresponding Gemcitabine intermediate. A product obtained with the method provided by the invention has an ee value being as high as 98% or above, the content of an erythro form product is high, and the obtained product does not need to be refined and can be directly used for next reaction.

PREPARATION OF GEMCITABINE AND INTERMEDIATES THEREOF

The present patent application relates to a process for the preparation gemcitabine or a salt thereof. More particularly it relates to preparation of 3,5- dihydroxy protected -2-deoxy-2,2-difluoro -1-oxoribose, an intermediate used in the preparation of gemcitabine and its salts by using cyclohexylidene or cyclopentylidene protecting group, with high yield and purity.