Sodium Carbonate → rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(1-propionyl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

HRID 587334ノート

反応式

HRID 587334 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:15][N:14]([C:25]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[O:26])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:43](Cl)(=[O:46])[CH2:44][CH3:45].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:15][N:14]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:43](=[O:46])[CH2:44][CH3:45])[CH2:29][CH2:28]3)=[O:26])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 10340Sodium CarbonateHCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 58303080[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

生成物 1

HCID 58303148rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(1-propionyl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester収率 40%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (200 mg, 0.41 mmol) in THF (2 mL) was added N,N-diisopropyl ethyl amine (208 μl, 1.21 mmol). After stirring for a period of 5 min propionyl chloride (53 μl, 0.61 mmol) was added. After stirring for 3 h at ambient temperature the reaction mixture was treated with an aqueous solution of sodium carbonate (1 M, 10 mL). The organic layer was separated and washed with brine (10 mL) and the aqueous layers were extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 80:20) afforded the title compound (88 mg, 40%) as a white solid. MS m/e: 550.3 [M]+.

後処理

  1. additionwas added
  2. customThe organic layer was separated
  3. washwashed with brine (10 mL)
  4. extractionthe aqueous layers were extracted with ethyl acetate (20 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated
  7. customPurification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 80:20)

出典と根拠

ORDレコード
ord-2ed48627d4ed478c8171d129e72fed30
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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