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

反応式

HRID 508106 の反応式
[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]

参加物

6

反応物 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

生成物 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}propanoate収率 50.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-d7b016c54a4f44269033270f83ab7064
出典データセット
uspto-grants-2010_08
特許番号
US07786165B2

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