Reacción #363937

Ecuación de reacción

N-methylmorpholine

L-alanine methyl ester hydrochloride

HOBT

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide

Boc-(D)-Methionine

→

Boc-(D)-Met-(L)-Ala-OMe

Rendimiento 77.1%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroSolvent was removed by evaporation
2. 2
   Otrothe residue was partitioned between dichloromethane (100 ml) and 5% aqueous acetic acid (50 ml)
3. 3
   Otrocrystallised
4. 4
   Otrowas removed by filtration
5. 5
   Otrothe organic layer was separated
6. 6
   Lavadowashed with aqueous sodium bicarbonate
7. 7
   Secadodried (MgSO4)
8. 8
   Otroevaporated
9. 9
   OtroThe residue (8.5 g) was purified by flash chromatography in a sinter funnel
10. 10
    Lavadoeluting with a mixture of dichloromethane and ether (0% to 100% ether)
11. 11
    workup.ADDITIONThe fractions containing product
12. 12
    Otroevaporated

Procedimiento

N-methylmorpholine (5.6 g), L-alanine methyl ester hydrochloride (3.9 g), HOBT (4.6 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (5.3 g) was added to a solution of Boc-(D)-Methionine (7 g, 0.028 mol) in dry DMF (50 ml). The mixture was stirred overnight. Solvent was removed by evaporation and the residue was partitioned between dichloromethane (100 ml) and 5% aqueous acetic acid (50 ml). On standing HOBT crystallised and was removed by filtration, and the organic layer was separated and washed with aqueous sodium bicarbonate, dried (MgSO4) and evaporated. The residue (8.5 g) was purified by flash chromatography in a sinter funnel eluting with a mixture of dichloromethane and ether (0% to 100% ether). The fractions containing product were combined and evaporated to give Boc-(D)-Met-(L)-Ala-OMe (7.2 g) as a gum which crystallised on standing; NMR (CDCl3): 1.4 (d, 3H), 1.45 (s, 9H), 1.95 (m, 1H), 2.1 (s, 3H), 2.1 (m, 1H), 2.6 (m, 2H), 3.75 (s,3H), 4.3 (bs, 1H), 4.6 (m, 1H), 5.3 (m, 1H), 6.9 (bs, 1H).

Fuente