Trifluoroacetic acid → rac-{4-[(3S,4R)-3-(3,4-Dichloro-phenyl)-4-methylamino-pyrrolidine-1-carbonyl]-piperidin-1-yl}-(1-methyl-cyclopropyl)-methanone

HRID 587309ノート

反応式

HRID 587309 の反応式
C(O[C:6](=O)[N:7]([C@@H:9]1[C@@H:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[CH2:12][N:11]([C:22]([CH:24]2[CH2:29][CH2:28][N:27]([C:30]([C:32]3([CH3:35])[CH2:34][CH2:33]3)=[O:31])[CH2:26][CH2:25]2)=[O:23])[CH2:10]1)C)(C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[Cl:21][C:16]1[CH:15]=[C:14]([C@@H:13]2[C@@H:9]([NH:7][CH3:6])[CH2:10][N:11]([C:22]([CH:24]3[CH2:29][CH2:28][N:27]([C:30]([C:32]4([CH3:35])[CH2:33][CH2:34]4)=[O:31])[CH2:26][CH2:25]3)=[O:23])[CH2:12]2)[CH:19]=[CH:18][C:17]=1[Cl:20]

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 58009304rac-{(3R,4S)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid tert-butyl ester

生成物 1

HCID 58009329rac-{4-[(3S,4R)-3-(3,4-Dichloro-phenyl)-4-methylamino-pyrrolidine-1-carbonyl]-piperidin-1-yl}-(1-methyl-cyclopropyl)-methanone収率 73%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Under an atmosphere of nitrogen to a solution of rac-{(3R,4S)-4-(3,4-dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid tert-butyl ester (3.02 g, 5.61 mmol) in dichloromethane (30 mL) was added at ambient temperature trifluoroacetic acid (4.3 mL, 56 mmol) and stirred for 20 h at this temperature. The reaction mixture was added slowly onto an aqueous solution of sodium carbonate (1M, 60 mL). The organic layer was separated and washed with brine (50 mL). The aqueous layers were extracted with dichloromethane (30 mL), dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate:methanol=50:50:0 to 0:90:10) afforded the title compound (1.79 g, 73%) as a light brown oil. MS m/e: 338.3 [M+H]+.

後処理

  1. customThe organic layer was separated
  2. washwashed with brine (50 mL)
  3. extractionThe aqueous layers were extracted with dichloromethane (30 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customPurification by chromatography (SiO2, heptane:ethyl acetate:methanol=50:50:0 to 0:90:10)

出典と根拠

ORDレコード
ord-cb18cb12e7d04fa8abb9d32ed87d93b6
出典データセット
uspto-grants-2016_01
特許番号
US09226916B2

反応ノート

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