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 1896095Notes

Reaction equation

HRID 1896095 reaction equation
[O:1]=[C:2]([N:23]1[CH2:28][CH2:27][N:26]2[C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][CH:31]=[C:25]2[CH2:24]1)[CH2:3][C@H:4]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14].[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>[O:1]=[C:2]([N:23]1[CH2:28][CH2:27][N:26]2[C:29]([C:32]([F:33])([F:34])[F:35])=[N:30][C:31]([Br:36])=[C:25]2[CH2:24]1)[CH2:3][C@H:4]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[C:9]([F:13])=[CH:8][C:7]=1[F:14]

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

tert-Butyl(R)-[3-oxo-1-(2,4,5-trifluoro-benzyl)-3-(3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazin-7-yl)-propyl]-carbamate 1m (20.0 g, 39.6 mmol) was dissolved in 300 mL of anhydrous ethanol, and N-bromosuccinimide (14.1 g, 79.2 mmol) was then added to the solution. 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 another one hour. The reaction mixture was filtered through a pad of coarse silica gel, and then the filtrate was concentrated under reduced pressure. The resulting residues were purified by silica gel column chromatography with system B as eluant to obtain the title compound 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)-propyl]-carbamate 1n (20.0 g, yield 86%) as a white solid. 1HNMR (400 MHz, CDCl3, ppm): δ 7.063 (m, 1H), 6.88 (m, 1H), 4.72 (s, 1H), 4.56 (s, 1H), 4.13 (m, 3H), 3.88 (m, 2H), 2.94 (m, 2H), 2.62 (m, 2H), 1.36 (s, 9H).

Workup

  1. stirringthe mixture was stirred for another one hour
  2. filtrationThe reaction mixture was filtered through a pad of coarse silica gel
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe resulting residues were purified by silica gel column chromatography with system B as eluant

Sources & evidence

ORD record
ord-172513d7867a4b82a536fc679719b71a
Source dataset
uspto-grants-2013_08
Patent number
US08518946B2

Reaction notes

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