Reaction #320521

Reaction equation

chlorotrimethylsilane

hexyllithium

hydrochloric acid

hexyllithium

methyl (S)-2-methoxycarbonylamino-3-phenyl-propionate

bromochloromethane

→

methyl (S)-(1-benzyl-3-chloro-2-oxo-propyl)-carbamate

Yield 70.0%

Solvents

hexane

tetrahydrofuran

water

tetrahydrofuran

Conditions

Workup

1. 1
   Temperaturewarmed to 22°
2. 2
   OtherThe phases were separated
3. 3
   Washthe organic phase was washed with saturated sodium chloride solution
4. 4
   Otherdried
5. 5
   Concentrationconcentrated
6. 6
   OtherThe residue was recrystallized from ethyl acetate and hexane
7. 7
   Otherthe crystallizate was dried

Procedure

15.4 ml of a 2.6 molar solution of hexyllithium in hexane were added dropwise at -80° C. to a solution of 9.50 g of methyl (S)-2-methoxycarbonylamino-3-phenyl-propionate in 60 ml of tetrahydrofuran. Subsequently, the mixture was treated with 5.60 ml of chlorotrimethylsilane. The resulting suspension was stirred and treated with 3.22 ml of bromochloromethane. Subsequently, 18.4 ml of hexyllithium solution were added. The solution was treated at -80° C. with 11 ml of 20% methanolic hydrochloric acid, warmed to 22° and diluted with 100 ml of water and 40 ml of tetrahydrofuran. The phases were separated and the organic phase was washed with saturated sodium chloride solution, dried and concentrated. The residue was recrystallized from ethyl acetate and hexane and the crystallizate was dried, there being obtained 7.20 g (70%) of pure methyl (S)-(1-benzyl-3-chloro-2-oxo-propyl)-carbamate, m.p. 122°-123° C. IR (KBr): 3336s (NH), 1737s and 1686s (C=O), 1535s (amide II).

Source