Ethyl chloroacetate → (R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl ester

HRID 1896096Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1896096
ClC[C:3]([O:5][CH2:6]C)=[O:4].C(=O)([O-])[O-].[K+].[K+].[O:14]=[C:15]([N:36]1[CH2:41][CH2:40][N:39]2[C:42]([C:46]([F:49])([F:48])[F:47])=[N:43][C:44](Br)=[C:38]2[CH2:37]1)[CH2:16][C@H:17]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:18][C:19]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:20]=1[F:27]>[CH-]=O.[CH-]=O.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Co].[Co+2].CO>[C:31]([O:30][C:29]([NH:28][C@H:17]([CH2:18][C:19]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:20]=1[F:27])[CH2:16][C:15]([N:36]1[CH2:41][CH2:40][N:39]2[C:42]([C:46]([F:49])([F:48])[F:47])=[N:43][C:44]([C:3]([O:5][CH3:6])=[O:4])=[C:38]2[CH2:37]1)=[O:14])=[O:35])([CH3:34])([CH3:33])[CH3:32]

Komponenten

6

Edukt 3

HCID 7751Ethyl chloroacetateHCID 11430Potassium CarbonateHCID 57518400(R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(1-bromo-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamic acid tert-butyl ester

Produkt 1

HCID 59548953(R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl esterAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 25049Dicobalt Octacarbonyl (stabilized with 1-5% Hexane)KatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

Refer to Journal of Organometallic Chemistry, 1985, 285(1-3), 293-303. Octacarbonyldicobalt (4.02 g, 11.76 mmol), ethyl chloroacetate (0.71 g, 5.88 mmol), potassium carbonate (1.62 g, 11.76 mmol) and 50 mL of methanol were added into the reaction flask. After stirring for 5 minutes, tert-butyl (R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(1-bromo-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-prop yl]-carbamate 1n (2.3 g, 3.92 mmol) was added. The reaction mixture was stirred at 60° C. for 2 hours and then concentrated under reduced pressure. The resulting residues were purified by silica gel column chromatography with system B as eluant to obtain the title compound methyl (R)-7-[3-tert-butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-formate 1p (1.1 g, yield 50%) as a white solid. MS m/z (ESI): 565.0 [M+1].

Aufarbeitung

  1. stirringThe reaction mixture was stirred at 60° C. for 2 hours
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting residues were purified by silica gel column chromatography with system B as eluant

Quellen und Nachweise

ORD-Eintrag
ord-7735ad5548ee4800946f60d869a0b6e3
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08518946B2

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