Reacción #11082

Ecuación de reacción

3-(trifluoromethyl)benzyl bromide

NaH

acid 1i

{6-[4-(tert-butoxycarbonylamino-imino-methyl)-benzylcarbamoyl]-4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-3-yl}-carbamic acid benzyl ester

THF

→

3-(trifluoromethyl)benzyl amine

Rendimiento 93.0%

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

Rendimiento 93.0%

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroquenched with the addition of 50 mL H2O
2. 2
   OtroThe volatile solvents were removed by rotary evaporation
3. 3
   Otrothe aqueous solution obtained
4. 4
   Otrowas partitioned with Et2O
5. 5
   ExtracciónThe organic phase was extracted with 20% sat. NaHCO3 (3×)
6. 6
   ExtracciónThe combined aqueous extract
7. 7
   Extracciónextracted with EtOAc (5×)
8. 8
   ExtracciónThe combined organic extract
9. 9
   Lavadowas washed (brine)
10. 10
    Secadodried (Na2SO4)
11. 11
    Concentraciónconcentrated

Procedimiento

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 aqueous 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 (25a), which was used in the following step without additional purification. MS (ESI) 488.3 (M+H+), 510.3 (M+Na+); 486.3 (M−H+).

Fuente