Ammonium Chloride → 1-acetyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester

HRID 221481Notes

Reaction equation

HRID 221481 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([C:23]([F:26])([F:25])[F:24])=[N:15][C:16]([C:17](=[O:22])N(OC)C)=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][Mg]Br.[Cl-].[NH4+]>O1CCCC1.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([C:23]([F:25])([F:26])[F:24])=[N:15][C:16]([C:17](=[O:22])[CH3:27])=[C:10]2[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 575184541-(methoxy-methyl-carbamoyl)-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl esterHCID 178418573HCID 178418573, compound

Product 1

HCID 575184551-acetyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl esterYield 91.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

1-(Methoxy-methyl-carbamoyl)-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester 27e (0.3 g, 0.79 mmol) was dissolved in 20 mL of tetrahydrofuran under stirring, and methylmagnesium bromide (1.13 mL, 1.58 mmol) was then added dropwise to the solution at 0° C. The reaction mixture was reacted at 0° C. for 1.5 hours and monitored by thin layer chromatography until the disappearance of the starting materials. 50 mL of saturated ammonium chloride and 10 mL of saturated brine were added to the reaction mixture. The mixture was extracted with ethyl acetate (50 mL×3). The combined organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 1-acetyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester 27f (0.24 g, yield 90%) as a yellow oil.

Workup

  1. customThe reaction mixture was reacted at 0° C. for 1.5 hours
  2. extractionThe mixture was extracted with ethyl acetate (50 mL×3)
  3. dry with materialThe combined organic phase was dried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8106e42eaaeb402cb493bf9f68c2d402
Source dataset
uspto-grants-2012_06
Patent number
US08207161B2

Reaction notes

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