Reaction #1431

Reaction equation

(3S-cis)-hexahydro-3-[[(1,1-dimethylethoxy)carbonyl]amino]-7-methyl-2H-azepin-2-one

lithium bis(trimethylsilyl)amide

ethyl bromoacetate

→

title product

(3S-cis)-Hexahydro-3-[[(1,1-dimethylethoxy)carbonyl]amino]-7-methyl-2-oxo-1H-azepine-1-acetic acid, ethyl ester

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Otherquenched with aqueous ammonium chloride
2. 2
   workup.ADDITIONdiluted with water
3. 3
   Extractionextracted twice with ethyl acetate
4. 4
   WashThe combined organic layers were washed with brine
5. 5
   Dryingdried (sodium sulfate)
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated to a yellow oil
8. 8
   Washeluting with 2:1 hexane/ethyl acetate, 750 mg

Procedure

A solution of (3S-cis)-hexahydro-3-[[(1,1-dimethylethoxy)carbonyl]amino]-7-methyl-2H-azepin-2-one [prepared as described in Example 64(f), 500 mg., 2.06 mmol.] in tetrahydrofuran (13 ml.) at room temperature under argon was treated dropwise with 1.0M lithium bis(trimethylsilyl)amide in tetrahydrofuran (2.7 ml., 2.7 mmol.) immediately followed by the dropwise addition of ethyl bromoacetate (0.47 ml., 4.21 mmol.). The resulting mixture was stirred for 30 minutes, quenched with aqueous ammonium chloride, diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate), filtered and concentrated to a yellow oil. Following flash chromatography (E Merck silica gel) eluting with 2:1 hexane/ethyl acetate, 750 mg. of title product was obtained as a light yellow oil; TLC (1:1 ethyl acetate:hexane) Rf =0.52.

Source