Reacción #51500

Ecuación de reacción

n-butyllithium

LDA

ICH2Cl

(2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid methyl ester

→

title compound

tert-butyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe mixture is cooled to −78°
2. 2
   Temperaturamaintaining an internal temperature below −60°
3. 3
   workup.ADDITIONOnce the addition
4. 4
   workup.ADDITIONis added dropwise
5. 5
   Temperaturamaintaining an internal temperature below about −60°
6. 6
   Otrothen quenched into 0° hydrochloric acid (IN)
7. 7
   workup.ADDITIONEthyl acetate is added
8. 8
   Otrothe phases are separated
9. 9
   Extracciónthe aqueous phase is extracted with ethyl acetate
10. 10
    LavadoThe combined organic phases are washed with saturated sodium bicarbonate
11. 11
    Secadodried over sodium sulfate
12. 12
    Filtraciónfiltered
13. 13
    Concentraciónconcentrated under reduced pressure

Procedimiento

ICH2Cl (3.54 g, 1.46 mL, 19.82 mmol, 1.25 equivalent) and THF (5 mL) are added to (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid methyl ester (II, EXAMPLE 1, 5 g, 15.86 mmol, 1 equivalent). The mixture is cooled to −78° and LDA (22.3 mL, 44.60 mmol, 2.25 equivalents, 2.0M) is added dropwise maintaining an internal temperature below −60°. Once the addition is complete, the contents are stirred for 30 min at −78° at which time n-butyllithium (15.3 mL, 19.82 mmol, 1.25 equivalents; 1.3M in hexanes) is added dropwise maintaining an internal temperature below about −60°. The reaction is stirred for 30 min then quenched into 0° hydrochloric acid (IN). Ethyl acetate is added and the phases are separated and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with saturated sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound, NMR (DMSO-d6) δ 7.47, 7.06-7.14, 4.78, 4.49, 3.20, 2.82 and 1.40; CMR (DMSO-d6) δ 200.87, 163.74, 161.20, 142.74, 112.80, 102.13, 79.04, 58.97, 47.72, 34.95 and 28.30.

Fuente