Water → ethyl 6-(N-(3-bromophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate

HRID 1424874ノート

反応式

HRID 1424874 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:11][C:12]1[CH:13]=[C:14]([NH:18][C:19]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:22]3[C:23]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[C:24]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)[O:25][C:21]=3[CH:20]=2)[CH:15]=[CH:16][CH:17]=1.[CH3:43][S:44](Cl)(=[O:46])=[O:45].O>C1COCC1.CCOC(C)=O>[Br:11][C:12]1[CH:13]=[C:14]([N:18]([C:19]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:22]3[C:23]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[C:24]([C:26]4[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=4)[O:25][C:21]=3[CH:20]=2)[S:44]([CH3:43])(=[O:46])=[O:45])[CH:15]=[CH:16][CH:17]=1

参加物

7

反応物 4

HCID 962WaterHCID 31297Methanesulfonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 71258359Ethyl 6-((3-bromophenyl)amino)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate

生成物 1

HCID 131732322ethyl 6-(N-(3-bromophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate収率 37.5%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A solution of lithium bis(trimethylsilyl)amide (1M in THF) (1.93 mL, 1.93 mmol) was added dropwise to a solution of ethyl 6-((3-bromophenyl)amino)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate (734 mg, 1.48 mmol) in THF (10 mL) at −78° C. The mixture was stirred for 45 minutes and then a solution of methanesulfonyl chloride (0.463 mL, 5.94 mmol) in THF (1.5 mL) was added at −78° C. After complete addition the reaction mixture was allowed to warm to room temperature overnight. Water and EtOAc were added. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (hexane:EtOAc) to give ethyl 6-(N-(3-bromophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)benzofuran-3-carboxylate (318 mg, 37%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1H) 8.03-8.13 (m, 2H) 7.62-7.66 (m, 1H) 7.59 (s, 1H) 7.43 (s, 4H) 7.30-7.39 (m, 1H) 4.26-4.41 (m, 2H) 3.42 (s, 3H) 2.12-2.26 (m, 1H) 1.28-1.37 (m, 3H) 0.71-1.14 (m, 4H) 0.41 (m, 1H). %). LCMS (m/z, ES+)=572, 574 (M+H, M+2).

後処理

  1. additionAfter complete addition the reaction mixture
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (hexane:EtOAc)

出典と根拠

ORDレコード
ord-82a436d764f84062b5704b1a97eb6386
出典データセット
uspto-grants-2015_01
特許番号
US08927593B2

反応ノート

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