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 587308Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 587308
[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]

Komponenten

7

Edukt 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

Produkt 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 esterAusbeute 75,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-079f1131149644fbb3df7cf49817e81c
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09226916B2

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