Methyl chloroacetate → 7-tert-Butyl 1-methyl 3-(trifluoromethyl)-5H,6H,7H,8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylate

HRID 1895638Notes

Reaction equation

HRID 1895638 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]2[C:20]([C:24]([F:27])([F:26])[F:25])=[N:21][C:22](Br)=[C:16]2[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].ClC[C:30]([O:32][CH3:33])=[O:31]>CO.[CH-]=O.[CH-]=O.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Co].[Co+2]>[CH3:33][O:32][C:30]([C:22]1[N:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[N:17]2[CH2:18][CH2:19][N:14]([C:12]([O:11][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:13])[CH2:15][C:16]=12)=[O:31]

Participants

6

Reactant 3

HCID 7295Methyl chloroacetateHCID 11430Potassium CarbonateHCID 57518451tert-butyl 1-bromo-3-(trifluoromethyl)-5H,6H,7H,8H-imidazo(1,5-a)pyrazine-7-carboxylate

Product 1

HCID 575184527-tert-Butyl 1-methyl 3-(trifluoromethyl)-5H,6H,7H,8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylateYield 67.8%

Reagents, catalysts & solvents 2

HCID 25049Dicobalt Octacarbonyl (stabilized with 1-5% Hexane)CatalystHCID 887MethanolSolvent

Procedure

Octacarbonyldicobalt (5.54 g, 16.2 mmol) and potassium carbonate (11.2 g, 81.1 mmol) was dissolved in 100 mL of methanol under stirring. The reaction mixture was stirred for 15 minutes at 60° C., and 1-bromo-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester 27b (3 g, 8.11 mmol) and methyl chloroacetate (5.25 g, 48.6 mmol) were then added to the solution. The reaction mixture was reacted for 6 hours under a carbon monoxide atmosphere and monitored by thin layer chromatography until the disappearance of the starting materials. After cooling to room temperature, the reaction mixture was filtered through a pad of silica gel, rinsed with methanol. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 1-methyl ester 27c (1.92 g, yield 67%) as a white solid. (Reference: J. Organomet. Chem., 1985, 293)

Workup

  1. stirringThe reaction mixture was stirred for 15 minutes at 60° C.
  2. customThe reaction mixture was reacted for 6 hours under a carbon monoxide atmosphere
  3. filtrationthe reaction mixture was filtered through a pad of silica gel
  4. washrinsed with methanol
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-48b8391e67f5428b86e6b99f05cbdd99
Source dataset
uspto-grants-2013_08
Patent number
US08513411B2

Reaction notes

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