p-Toluenesulfonic acid → N-[[2-(tert-butyldiphenylsilyloxy)ethoxy]methyl]-5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxamide

HRID 1641749Notes

Reaction equation

HRID 1641749 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:22]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23])[C:10]1[C:11]([CH3:21])=[CH:12][C:13]([C:16]([NH:18][CH2:19][OH:20])=[O:17])=[N:14][CH:15]=1.[Si:32]([O:49][CH2:50][CH2:51]O)([C:45]([CH3:48])([CH3:47])[CH3:46])([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[Si:32]([O:49][CH2:50][CH2:51][O:20][CH2:19][NH:18][C:16]([C:13]1[CH:12]=[C:11]([CH3:21])[C:10]([CH:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])[S:22]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)(=[O:24])=[O:23])=[CH:15][N:14]=1)=[O:17])([C:45]([CH3:46])([CH3:47])[CH3:48])([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 119996905-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-N-(1-hydroxymethyl)-4-methylpyridine-2-carboxamideHCID 151562692-((tert-Butyldiphenylsilyl)oxy)ethanol

Product 1

HCID 57736459N-[[2-(tert-butyldiphenylsilyloxy)ethoxy]methyl]-5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxamideYield 51%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
60 °C

Procedure

5-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]meth yl]-N-(1-hydroxymethyl)-4-methylpyridine-2-carboxamide (113 mg, 0.251 mmol) obtained in Example 85, and a solution of 2-(tert-butyldiphenylsilyloxy)ethanol (136 mg, 0.453 mmol) and p-toluenesulfonic acid (10 mg) in benzene (5 ml) were stirred for 3 hours with heating to 60° C. The reaction solution was returned to room temperature, and then was concentrated under reduced pressure. Ethyl acetate was added to the resulting concentration residue, and the mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was subjected to flash silica gel column chromatography, and the fraction obtained from an elution with 25% ethyl acetate/hexane was concentrated under reduced pressure, to obtain the title compound (93 mg, 0.127 mmol, 51%) as an amorphous substance.

Workup

  1. customwas returned to room temperature
  2. concentrationwas concentrated under reduced pressure
  3. additionEthyl acetate was added to the resulting concentration residue
  4. washthe mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. concentrationThe resulting concentration residue
  9. customthe fraction obtained from an elution with 25% ethyl acetate/hexane
  10. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-597b71620be3453a92ab4d37c0f8f156
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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