Formic Acid → 4-[4-[(3E)-1-(4-chloro-2-fluorophenyl)-3-hydroxyimino-3-(2-methyl-4-pyridinyl)propyl]phenyl]thiophene-2-carboxylic acid

HRID 1617610노트

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HRID 1617610 반응식
C([O:3][C:4]([C:6]1[S:7][CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([CH:17]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=3[F:36])[CH2:18]/[C:19](=[N:27]\[OH:28])/[C:20]3[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=3)=[CH:13][CH:12]=2)[CH:10]=1)=[O:5])C.[Li+].[OH-].C(O)=O>O1CCOCC1.O>[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([CH:17]([C:14]2[CH:13]=[CH:12][C:11]([C:9]3[CH:10]=[C:6]([C:4]([OH:5])=[O:3])[S:7][CH:8]=3)=[CH:16][CH:15]=2)[CH2:18]/[C:19](=[N:27]\[OH:28])/[C:20]2[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=2)=[C:30]([F:36])[CH:31]=1

참가 물질

5

반응물 3

HCID 284Formic AcidHCID 3939Lithium Hydroxide2회HCID 136167036ethyl 4-[4-[(3E)-1-(4-chloro-2-fluorophenyl)-3-hydroxyimino-3-(2-methyl-4-pyridinyl)propyl]phenyl]thiophene-2-carboxylate

생성물 1

HCID 1361669614-[4-[(3E)-1-(4-chloro-2-fluorophenyl)-3-hydroxyimino-3-(2-methyl-4-pyridinyl)propyl]phenyl]thiophene-2-carboxylic acid수율 98.6%

시약·촉매·용매 1

HCID 218864351,4-Dioxane--water (1/1)용매

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온도
100 °C

실험 절차

To a solution of 4-{4-[1-(4-chloro-2-fluoro-phenyl)-3-[(E)-hydroxyimino]-3-(2-methyl-pyridin-4-yl)-propyl]-phenyl}-thiophene-2-carboxylic acid ethyl ester (15 mg) in dioxane/water (1.5 mL, 1:1) was added LiOH (7.2 mg) and the reaction mixture heated by microwave irradiation to 100° C. for 30 min. Formic acid was added to neutralize LiOH and the solvent mixture removed by evaporation under reduced pressure. Purification of the crude reaction product by silica column chromatography eluting with a mixture of dichloromethane/methanol (95:5, containing 4% formic acid) provided 14 mg (98%) of the title compound as an off-white powder, MS (ESI+): m/z=495.1 [M+H]+.

후처리

  1. customthe solvent mixture removed by evaporation under reduced pressure
  2. customPurification of the crude
  3. customreaction product by silica column chromatography
  4. washeluting with a mixture of dichloromethane/methanol (95:5, containing 4% formic acid)

출처 및 근거

ORD 기록
ord-adb77e2479554683b7bd2a20b6c8a17d
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765730B2

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