Reaktion #51500

Reaktionsgleichung

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

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture is cooled to −78°
2. 2
   Temperaturmaintaining an internal temperature below −60°
3. 3
   workup.ADDITIONOnce the addition
4. 4
   workup.ADDITIONis added dropwise
5. 5
   Temperaturmaintaining an internal temperature below about −60°
6. 6
   Sonstigethen quenched into 0° hydrochloric acid (IN)
7. 7
   workup.ADDITIONEthyl acetate is added
8. 8
   Sonstigethe phases are separated
9. 9
   Extraktionthe aqueous phase is extracted with ethyl acetate
10. 10
    WaschenThe combined organic phases are washed with saturated sodium bicarbonate
11. 11
    Trocknendried over sodium sulfate
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated under reduced pressure

Vorschrift

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.

Quelle