Sodium hydride → (S)-3-{[(benzyloxy)carbonyl][3-(trifluoromethyl)benzyl]amino}-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxylic Acid

HRID 481247Notes

Reaction equation

HRID 481247 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:17](=[O:18])[N:16]2[C@H:19]([C:22]([OH:24])=[O:23])[CH2:20][CH2:21][C:15]2=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30]Br.[H-].[Na+]>C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[CH2:1]([O:8][C:9]([N:11]([CH2:30][C:29]1[CH:32]=[CH:33][CH:34]=[C:27]([C:26]([F:25])([F:35])[F:36])[CH:28]=1)[C:12]1[C:17](=[O:18])[N:16]2[C@H:19]([C:22]([OH:24])=[O:23])[CH2:20][CH2:21][C:15]2=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 53717804(6S)-3-{[(Benzyloxy)carbonyl]amino}-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxylic acid

Product 1

HCID 57444827(S)-3-{[(benzyloxy)carbonyl][3-(trifluoromethyl)benzyl]amino}-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-6-carboxylic AcidYield 93%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of acid 1i (4.50 g, 13.7 mmol) in 70 mL THF at 0° C., was added 3-(trifluoromethyl)benzyl bromide (8.35 mL, 54.7 mmol), NaH (60% dispersion in oil, 1.64 g, 41.4 mmol), and TBAI (100 mg, catalytic). The reaction was stirred at rt for 15 h, then quenched with the addition of 50 mL H2O. The volatile solvents were removed by rotary evaporation and the aqueous solution obtained was partitioned with Et2O. The organic phase was extracted with 20% sat. NaHCO3 (3×). The combined organic extract was acidified with 1N HCl and extracted with EtOAc (5×). The combined organic extract was washed (brine), dried (Na2SO4), and concentrated to afford 6.18 g (93%) of the 3-(trifluoromethyl)benzyl amine (12a), which was used in the following step without additional purification.

Workup

  1. customquenched with the addition of 50 mL H2O
  2. customThe volatile solvents were removed by rotary evaporation
  3. customthe aqueous solution obtained
  4. customwas partitioned with Et2O
  5. extractionThe organic phase was extracted with 20% sat. NaHCO3 (3×)
  6. extractionThe combined organic extract
  7. extractionextracted with EtOAc (5×)
  8. extractionThe combined organic extract
  9. washwas washed (brine)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-46e3b06cb32c4e5bbfac6044a574b0da
Source dataset
uspto-grants-2003_11
Patent number
US06653295B2

Reaction notes

Loading…