Ethyl Glycolate → Ethyl [[[[5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridin-2-yl]carbonyl]amino]methoxy]acetate

HRID 1641763Notes

Reaction equation

HRID 1641763 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.O[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[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:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)(=[O:24])=[O:23])[C:10]1[C:11]([CH3:21])=[CH:12][C:13]([C:16]([NH:18][CH2:19][O:20][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[O:17])=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 12184Ethyl GlycolateHCID 521998p-Toluenesulfonic acid monohydrateHCID 119996905-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-N-(1-hydroxymethyl)-4-methylpyridine-2-carboxamide

Product 1

HCID 57736550Ethyl [[[[5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridin-2-yl]carbonyl]amino]methoxy]acetateYield 35%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-N-(hydroxymethyl)-4-methylpyridine-2-carboxamide (421 mg, 0.935 mmol) obtained from Example 85, ethyl hydroxyacetate (106 μl, 1.12 mmol), p-toluenesulfonic acid monohydrate (18 mg, 0.094 mmol) in benzene (10 ml) was heated to reflux for 30 minutes. The reaction solution was returned to room temperature, and then was concentrated under reduced pressure. Saturated aqueous sodium hydrogencarbonate was added to the resulting concentration residue, and the mixture was extracted from ethyl acetate. The organic layer was washed with saturated brine, 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 35% ethyl acetate/hexane was concentrated under reduced pressure, to obtain the title compound (175 mg, 0.326 mmol, 35%) as a white solid.

Workup

  1. temperatureto reflux for 30 minutes
  2. customwas returned to room temperature
  3. concentrationwas concentrated under reduced pressure
  4. additionSaturated aqueous sodium hydrogencarbonate was added to the resulting concentration residue
  5. extractionthe mixture was extracted from ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. concentrationThe resulting concentration residue
  11. customthe fraction obtained from an elution with 35% ethyl acetate/hexane
  12. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-eed765b52e4347569ccbd822a30c45af
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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