1-Fluoro-4-(isocyanatomethyl)benzene → 1,1-Dicyclopropyl-N-[(4-fluorophenyl)methyl]-tetrahydro-3-oxo-3H-oxazolo[3,4-a]pyrazine-7(1H)-carboxamide

HRID 1713526Notes

Reaction equation

HRID 1713526 reaction equation
C1(COC([N:11]2[CH2:16][CH2:15][N:14]3[C:17](=[O:26])[O:18][C:19]([CH:23]4[CH2:25][CH2:24]4)([CH:20]4[CH2:22][CH2:21]4)[CH:13]3[CH2:12]2)=O)C=CC=CC=1.[F:27][C:28]1[CH:37]=[CH:36][C:31]([CH2:32][N:33]=[C:34]=[O:35])=[CH:30][CH:29]=1>C(O)C.[C].[Pd]>[CH:23]1([C:19]2([CH:20]3[CH2:22][CH2:21]3)[CH:13]3[CH2:12][N:11]([C:34]([NH:33][CH2:32][C:31]4[CH:30]=[CH:29][C:28]([F:27])=[CH:37][CH:36]=4)=[O:35])[CH2:16][CH2:15][N:14]3[C:17](=[O:26])[O:18]2)[CH2:25][CH2:24]1

Participants

5

Reactant 2

HCID 27333761-Fluoro-4-(isocyanatomethyl)benzeneHCID 68422186(Phenylmethyl)1,1-dicyclopropyl-tetrahydro-3-oxo-3H-oxazolo[3,4-a]pyrazine-7(1H)-carboxylate

Product 1

HCID 231219031,1-Dicyclopropyl-N-[(4-fluorophenyl)methyl]-tetrahydro-3-oxo-3H-oxazolo[3,4-a]pyrazine-7(1H)-carboxamideYield 87%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolvent

Procedure

(Phenylmethyl)1,1-dicyclopropyl-tetrahydro-3-oxo-3H-oxazolo[3,4-a]pyrazine-7(1H)-carboxylate (0.18 g, 0.50 mmol) was dissolved in ethanol (10 mL). 10% Palladium carbon (17 mg) was added thereto, and the mixture was stirred under hydrogen atmosphere at room temperature overnight. The reaction solution was filtered through Celite, the Celite was washed with ethanol, and the filtrate was concentrated under reduced pressure. The resulting 1,1-dicyclopropyl-hexahydro-3H-oxazolo[3,4-a]pyrazin-3-one was dissolved in tetrahydrofuran (10 mL). (4-Fluoro)benzyl isocyanate (0.25 mL, 2.0 mmol) was added thereto, and the mixture was stirred at 50° C. for 4 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified with silica gel column chromatography (hexane:ethyl acetate=1:1 to 1:4) to obtain the title compound (0.16 g, 87% yield from (phenylmethyl) 1,1-dicyclopropyl-tetrahydro-3-oxo-3H-oxazolo[3,4-a]pyrazine-7(1H)-carboxylate).

Workup

  1. filtrationThe reaction solution was filtered through Celite
  2. washthe Celite was washed with ethanol
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe resulting 1,1-dicyclopropyl-hexahydro-3H-oxazolo[3,4-a]pyrazin-3-one was dissolved in tetrahydrofuran (10 mL)
  5. stirringthe mixture was stirred at 50° C. for 4 hours
  6. concentrationThe reaction solution was concentrated under reduced pressure
  7. customthe residue was purified with silica gel column chromatography (hexane:ethyl acetate=1:1 to 1:4)

Sources & evidence

ORD record
ord-4624d882f6804bfc8a6e39a5595b56cc
Source dataset
uspto-grants-2010_09
Patent number
US07795267B2

Reaction notes

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