Lithium Hydroxide → (S)-2-(7-(tert-butoxycarbonyl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamido)-3,3-dimethylbutanoic acid

HRID 535938Notes

Reaction equation

HRID 535938 reaction equation
C[O:2][C:3](=[O:34])[C@@H:4]([NH:9][C:10]([C:12]1[N:13]=[C:14]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][C:16]=12)=[O:11])[C:5]([CH3:8])([CH3:7])[CH3:6].[OH-].[Li+]>C1COCC1.O>[C:24]([O:23][C:21]([N:18]1[CH2:19][CH2:20][N:15]2[C:14]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[N:13][C:12]([C:10]([NH:9][C@@H:4]([C:5]([CH3:7])([CH3:8])[CH3:6])[C:3]([OH:34])=[O:2])=[O:11])=[C:16]2[CH2:17]1)=[O:22])([CH3:25])([CH3:26])[CH3:27]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 57635284(S)-tert-butyl 1-(1-methoxy-3,3-dimethyl-1-oxobutan-2-ylcarbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

Product 1

HCID 57635146(S)-2-(7-(tert-butoxycarbonyl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamido)-3,3-dimethylbutanoic acidYield 86.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Intermediate 22A (2.73 g, 5.80 mmol) was dissolved in THF (20 mL) and cooled to 0° C. Lithium hydroxide (0.70 g, 29 mmol) solution in water (4 mL) was added and the mixture was stirred on ice bath for 6 hours. The mixture was concentrated under reduced pressure, cooled in an ice bath and acidified to pH 4 with 1N HCl. The resulting white precipitate was filtered, washed with water and dried in a vacuum oven at 40° C. to provide Intermediate 22B (2.29 g, 86%) as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ: 0.97 (s, 9H), 1.44 (s, 9H), 3.67 (m, 2H), 4.14 (t, 2H), 4.48 (d, 1H), 4.84 (s, 2H), 7.49 (m, 3H), 7.72 (m, 2H); LCMS (+ESI) m/z 457.2 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. temperaturecooled in an ice bath
  3. filtrationThe resulting white precipitate was filtered
  4. washwashed with water
  5. customdried in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-ca789f9269a34ee7896e2488937ed645
Source dataset
uspto-grants-2014_10
Patent number
US08859538B2

Reaction notes

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