Sodium Bicarbonate → HCID 178462402, compound

HRID 480934Notes

Reaction equation

HRID 480934 reaction equation
[CH:1]([C:3]1[CH:25]=[CH:24][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]([F:23])([F:22])[CH:19]([F:21])[F:20])=[CH:12][CH:11]=2)=[O:8])=[CH:5][CH:4]=1)=[O:2].[F:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[C@:34]([OH:49])([C@H:41]([S:43][CH:44]([CH2:47]O)[CH2:45][OH:46])[CH3:42])[CH2:35][N:36]1[CH:40]=[N:39][CH:38]=[N:37]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>O1CCCC1.ClCCl>[F:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[C@@:34]([OH:49])([CH2:35][N:36]1[CH:40]=[N:39][CH:38]=[N:37]1)[C@H:41]([S:43][C@@H:44]1[CH2:45][O:46][C@@H:1]([C:3]2[CH:4]=[CH:5][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]([F:22])([F:23])[CH:19]([F:20])[F:21])=[CH:12][CH:11]=3)=[O:8])=[CH:24][CH:25]=2)[O:2][CH2:47]1)[CH3:42]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 10594623(2R,3R)-2-(2,4-difluorophenyl)-3-[[1-(hydroxymethyl)-2-hydroxyethyl]-thio]-1-(1H-1,2,4-triazol-1-yl)-2-butanolHCID 187662944-Formyl-4'-(2,2,3,3-tetrafluoropropoxy)benzanilide

Product 1

HCID 178462402HCID 178462402, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Molecular sieve 4A (3 g) was added to a mixture of 4-formyl-4′-(2,2,3,3-tetrafluoropropoxy)benzanilide (300 mg, 0.84 mmol) obtained in example 1 (1), (2R,3R)-2-(2,4-difluorophenyl)-3-[[1-(hydroxymethyl)-2-hydroxyethyl]thio]-1-(1H-1,2,4-triazol-1-yl)-2-butanol (disclosed in Japanese Patent Application Publication No. Hei-8-333350; 253 mg, 0.70 mmol), p-toluenesulfonic acid monohydrate (160 mg, 0.84 mmol) in anhydrous tetrahydrofuran (10 ml) and anhydrous dichloromethane (5 ml). The resulting mixture was stirred at room temperature for two days. Aqueous sodium hydrogencarbonate solution was added to the reaction mixture at 0° C., and the mixture was filtered to remove the molecular sieve. The filtrate was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting oily residue was chromatographed on a silica gel column using ethyl acetate-hexane (2:1) as the eluant to afford the trans isomer of the title compound (87 mg, yield 18%) as a white solid and then using ethyl acetate-hexane (4:1) as the eluant to give the cis isomer (55 mg, yield 11%) as a colorless oil. The trans isomer was recrystallized from ethyl acetate-isopropyl ether to give white powdery crystals.

Workup

  1. filtrationthe mixture was filtered
  2. customto remove the molecular sieve
  3. customThe filtrate was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting oily residue was chromatographed on a silica gel column

Sources & evidence

ORD record
ord-9eaa63cec1424f9ba801d81483afd246
Source dataset
uspto-grants-2003_11
Patent number
US06653330B2

Reaction notes

Loading…