Potassium Carbonate → (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

HRID 221428Notes

Reaction equation

HRID 221428 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]([CH2:25][C:26]1[CH:31]=[C:30]([F:32])[C:29]([F:33])=[CH:28][C:27]=1[F:34])[CH2:9][C:10](=[O:24])[N:11]1[CH2:16][CH2:15][N:14]2[C:17]([C:20]([F:23])([F:22])[F:21])=[N:18][CH:19]=[C:13]2[CH2:12]1)([CH3:4])([CH3:3])[CH3:2].[Br:36]N1C(=O)CCC1=O.C(=O)([O-])[O-].[K+].[K+].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C(O)C>[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]([CH2:25][C:26]1[CH:31]=[C:30]([F:32])[C:29]([F:33])=[CH:28][C:27]=1[F:34])[CH2:9][C:10](=[O:24])[N:11]1[CH2:16][CH2:15][N:14]2[C:17]([C:20]([F:22])([F:21])[F:23])=[N:18][C:19]([Br:36])=[C:13]2[CH2:12]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 67184N-bromobutanimideHCID 90495Di-tert-butyl dicarbonateHCID 57518397HCID 57518397, compound

Product 1

HCID 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 esterYield 86.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamic acid tert-butyl ester 1l (20.0 g, 39.6 mmol) was dissolved in 300 mL of anhydrous ethanol under stirring, and 1-bromo-2,5-pyrrolidinedione (14.1 g, 79.2 mmol) was then added to the solution at room temperature. After stirring for an hour, potassium carbonate (10.9 g, 79.2 mmol) and di-tert-butyl dicarbonate (8.6 g, 39.6 mmol) were added to the mixture, and the mixture was stirred for an hour and monitored by thin layer chromatography until the disappearance of the starting materials. The reaction mixture was filtered through a pad of coarse silica gel to remove potassium carbonate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (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 1m (20.0 g, yield 86%) as a white solid.

Workup

  1. stirringAfter stirring for an hour
  2. stirringthe mixture was stirred for an hour
  3. filtrationThe reaction mixture was filtered through a pad of coarse silica gel
  4. customto remove potassium carbonate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3aa4535210ed42bb9cbd79c9d540b63f
Source dataset
uspto-grants-2012_06
Patent number
US08207161B2

Reaction notes

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