Thioglycolic Acid → ethyl 3-{2-fluoro-4-[({4'-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)amino]phenyl}propanoate

HRID 508106

반응식

HRID 508106 반응식
[F:1][C:2]1[CH:7]=[C:6]([N:8]([CH2:21][C:22]2[CH:23]=[C:24]([C:28]3[C:33]([CH3:34])=[CH:32][C:31]([O:35][CH2:36][C:37]4([OH:44])[CH2:42][CH2:41][S:40](=[O:43])[CH2:39][CH2:38]4)=[CH:30][C:29]=3[CH3:45])[CH:25]=[CH:26][CH:27]=2)S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[CH:5]=[CH:4][C:3]=1[CH2:46][CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49].SCC(O)=O.O.[OH-].[Li+]>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([NH:8][CH2:21][C:22]2[CH:23]=[C:24]([C:28]3[C:29]([CH3:45])=[CH:30][C:31]([O:35][CH2:36][C:37]4([OH:44])[CH2:42][CH2:41][S:40](=[O:43])[CH2:39][CH2:38]4)=[CH:32][C:33]=3[CH3:34])[CH:25]=[CH:26][CH:27]=2)[CH:5]=[CH:4][C:3]=1[CH2:46][CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49]

참가 물질

6

반응물 3

HCID 1133Thioglycolic AcidHCID 168937Lithium hydroxide, monohydrateHCID 68718060ethyl 3-(2-fluoro-4-{({4'-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate

생성물 1

HCID 59434131ethyl 3-{2-fluoro-4-[({4'-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2',6'-dimethylbiphenyl-3-yl}methyl)amino]phenyl}propanoate수율 50.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of ethyl 3-(2-fluoro-4-{({4′-[(4-hydroxytetrahydro-2H-thiopyran-4-yl)methoxy]-2′,6′-dimethylbiphenyl-3-yl}methyl) [(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (2.24 g, 3.04 mmol) in ethyl acetate (15 mL) was added m-chloroperbenzoic acid (70%, 0.46 g, 1.88 mmol) under stirring at 0° C., and the mixture was stirred at room temperature for 3 days. The reaction mixture was washed with 1 M aqueous sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1-ethyl acetate-ethyl acetate/methanol=17/3) to give ethyl 3-(2-fluoro-4-{({4′-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2′,6′-dimethylbiphenyl-3-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (1.36 g, yield 60%) as a colorless amorphous powder. To a solution of the obtained ethyl 3-(2-fluoro-4-{({4′-[(4-hydroxy-1-oxidotetrahydro-2H-thiopyran-4-yl)methoxy]-2′,6′-dimethylbiphenyl-3-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}phenyl)propanoate (1.36 g, 1.81 mmol) and mercaptoacetic acid (0.38 mL, 5.43 mmol) in N,N-dimethylformamide (10 mL) was added lithium hydroxide monohydrate (0.46 g, 10.86 mmol) under stirring at room temperature, and the mixture was stirred at the same temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogencarbonate and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1-ethyl acetate) to give the title compound (0.52 g, yield 50%) as a colorless oil.

후처리

  1. stirringthe mixture was stirred at the same temperature for 3 hr
  2. washwashed with saturated aqueous sodium hydrogencarbonate and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=9/1-ethyl acetate)

출처 및 근거

ORD 기록
ord-d7b016c54a4f44269033270f83ab7064
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786165B2

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