Diisopropylethylamine → 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

HRID 587308ノート

反応式

HRID 587308 の反応式
[C:1]([O:5][C:6](=[O:22])[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][NH:11][CH2:10]1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[CH3:32][C:33]1([C:36]([N:38]2[CH2:43][CH2:42][CH:41]([C:44](O)=[O:45])[CH2:40][CH2:39]2)=[O:37])[CH2:35][CH2:34]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:22])[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:44]([CH:41]2[CH2:40][CH2:39][N:38]([C:36]([C:33]3([CH3:32])[CH2:35][CH2:34]3)=[O:37])[CH2:43][CH2:42]2)=[O:45])[CH2:10]1)[CH3:8])([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58009331Rel-tert-butyl ((3R,4S)-4-(3,4-dichlorophenyl)pyrrolidin-3-yl)(methyl)carbamateHCID 594381681-(1-Methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid

生成物 1

HCID 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収率 75.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid tert-butyl ester (2.78 g, 7.56 mmol) in DMF (28 mL) were added at 0° C. N,N-diisopropyl ethyl amine (8.26 mL, 48.2 mmol), 1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid (2.78 g, 8.04 mmol), 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (3.67 g, 9.65 mmol). The resulting solution was stirred for 6 h at ambient temperature. After diluting with EtOAc (50 mL) the solution was washed twice with water (50 mL) and brine (50 mL). The aqueous layers were extracted with EtOAc (50 mL) and dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate:methanol=80:20:0 to 0:90:10) afforded the title compound (3.06 g, 75%) as a light brown foam. MS m/e: 538.3 [M+H]+.

後処理

  1. washwas washed twice with water (50 mL) and brine (50 mL)
  2. extractionThe aqueous layers were extracted with EtOAc (50 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate:methanol=80:20:0 to 0:90:10)

出典と根拠

ORDレコード
ord-079f1131149644fbb3df7cf49817e81c
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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