Triethylamine → 1-(2-Chloro-phenylcarbamoyl)-3-(4'-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester

HRID 2060293ノート

反応式

HRID 2060293 の反応式
C(N(CC)CC)C.[CH2:8]([O:10][C:11]([C:13]1([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)[CH2:17][CH2:16][NH:15][CH2:14]1)=[O:12])[CH3:9].[Cl:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[N:40]=[C:41]=[O:42]>ClCCl>[CH2:8]([O:10][C:11]([C:13]1([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=3)=[CH:22][CH:21]=2)[CH2:17][CH2:16][N:15]([C:41](=[O:42])[NH:40][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[Cl:33])[CH2:14]1)=[O:12])[CH3:9]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 76833Chlorophenyl isocyanateHCID 593221953-(4'-Fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester

生成物 1

HCID 593221711-(2-Chloro-phenylcarbamoyl)-3-(4'-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester収率 91.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

Triethylamine (0.23 mL, 1.67 mmol) was added to a stirred solution of 3-(4′-fluoro-biphenyl-4-yloxymethyl)-pyrrolidine-3-carboxylic acid ethyl ester (see Preparation 65) (185 mg, 0.54 mmol) in dichloromethane (10 mL) and the resulting mixture cooled to 0° C. 2-Chloro phenyl isocyanate (0.065 mL, 0.54 mmol) was added and the reaction mixture stirred at room temperature for 16 hours. The mixture was partitioned between water (25 mL) and dichloromethane (25 mL). The organic layer was separated, washed brine (25 mL), dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with 25% ethyl acetate in hexane to afford the title compound as a colourless liquid (245 mg, 91%).

後処理

  1. customThe mixture was partitioned between water (25 mL) and dichloromethane (25 mL)
  2. customThe organic layer was separated
  3. washwashed brine (25 mL)
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with 25% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-ce571c14454445968747c3253c9e4aa7
出典データセット
uspto-grants-2012_10
特許番号
US08278343B2

反応ノート

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