Reacción #78246

Ecuación de reacción

L-proline

trans-N-Boc-4-hydroxy-L-proline methyl ester

sodium hydride

4-bromobenzyl bromide

→

trans-N-Boc-4-(4-bromo-benzyloxy)-L-proline

Rendimiento 30.6%

Disolventes

water

THF

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas prepared
2. 2
   TemperaturaThe reaction mixture was refluxed for 3 hours
3. 3
   Extracciónextracted with EtOAc
4. 4
   Extracciónextracted with DCM
5. 5
   LavadoThe combined organic extracts were washed with water
6. 6
   Secadodried over MgSO4
7. 7
   Otroevaporated under reduced pressure

Procedimiento

The compound of formula (P5), wherein R′ is 4-Bromo and the bonds linking the benzyloxy and methyl ester groups (depicted in P5 as wavy bonds) define the trans, L-proline configuration (2S,4R) was prepared as follows. To a suspension of sodium hydride (60% in oil) (0.12 g) (1.5 eq.) in 5 mL of dry THF was added trans-N-Boc-4-hydroxy-L-proline methyl ester (0.5 g) in 5 mL of dry THF. The reaction mixture was stirred for 45 minutes and a solution of 4-bromobenzyl bromide (0.75 g) (1.5 eq.) in 5 mL of dry THF was added. The reaction mixture was refluxed for 3 hours. After cooling to RT, the reaction mixture was diluted with water and extracted with EtOAc. The aqueous layer was acidified and extracted with DCM. The combined organic extracts were washed with water, dried over MgSO4, and evaporated under reduced pressure to afford trans-N-Boc-4-(4-bromo-benzyloxy)-L-proline (0.25 g). NMR (CDCl3, 200 MHz): 7.47 (2H, d), 7.2 (2H, d), 4.50-4.30 (3H, m), 4.25-4.1 (1H, m), 3.75 (3H, s), 3.8-3.5 (2H, m), 2.5-2.3 (1H, m), 2.15-1.95 (1H, m), 1.5-1.35 (9H).

Fuente