4-Fluorobenzoic Acid → 4-fluoro-N-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)benzamide

HRID 1895901ノート

反応式

HRID 1895901 の反応式
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([S:9]([N:12]2[CH2:17][CH2:16][CH:15]([O:18][NH2:19])[CH2:14][CH2:13]2)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.ON1C2C=CC=CC=2N=N1.[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](O)=[O:38])=[CH:35][CH:34]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37]([NH:19][O:18][CH:15]2[CH2:14][CH2:13][N:12]([S:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:20])[F:21])[CH:4]=3)(=[O:11])=[O:10])[CH2:17][CH2:16]2)=[O:38])=[CH:35][CH:34]=1

参加物

6

反応物 4

HCID 99734-Fluorobenzoic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67118429O-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yl)hydroxylamine

生成物 1

HCID 445532904-fluoro-N-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)benzamide収率 81%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

1-(3-Dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (138 mg, 0.72 mmol) was added to a solution of O-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yl)hydroxylamine (195 mg, 0.60 mmol), 1-hydroxybenzotriazole (97.0 mg, 0.72 mmol), 4-fluorobenzoic acid (84.0 mg, 0.60 mmol) and N,N-diisopropylethylamine (233 mg, 1.80 mmol) in N,N-dimethylformamide (8 ml). The reaction mixture was stirred at room temperature for 17 hours and quenched with H2O (50 ml) and aqueous 1 N HCl solution (pH=3). The aqueous phase was extracted with CH2Cl2 (20 ml×3) and the combined organic phase was washed with aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/petroleum ether: 50/50) to give 4-fluoro-N-(1-(3-(trifluoromethyl)phenylsulfonyl)piperidin-4-yloxy)benzamide (217 mg, 81%) as a white solid: LCMS: 447 [M+1]+. 1H NMR (DMSO-d6) δ: 1.71 (m, 2H), 1.88 (m, 2H), 3.07 (m, 4H), 3.97 (t, 1H), 7.27 (t, 2H), 7.74 (m, 2H), 7.98 (m, 2H), 8.10 (m, 2H), 11.4 (s, 1H).

後処理

  1. customquenched with H2O (50 ml) and aqueous 1 N HCl solution (pH=3)
  2. extractionThe aqueous phase was extracted with CH2Cl2 (20 ml×3)
  3. washthe combined organic phase was washed with aqueous NaHCO3 solution and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ethyl acetate/petroleum ether: 50/50)

出典と根拠

ORDレコード
ord-5064ca088829443195395655d8c655c4
出典データセット
uspto-grants-2013_08
特許番号
US08518934B2

反応ノート

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