Reaction #1284

Reaction equation

potassium hydroxide

Ethyl bromoacetate

ethyl bromoacetate

(3R-cis)-tetrahydro-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepin-5(4H)-one

→

(3R-cis)-Tetrahydro-5-oxo-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepine-4(5H)-acetic acid, ethyl ester

Solvents

ethyl acetate

—

hexanes

tetrahydrofuran

ethyl acetate

magnesium sulfate

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred cold for two hours
2. 2
   workup.STIRRINGThe mixture was stirred cold for an additional two hours
3. 3
   workup.ADDITIONwas added
4. 4
   FiltrationThe reaction mixture was filtered through a magnesium sulfate pad
5. 5
   Washthe pad was washed several times with ethyl acetate
6. 6
   workup.ADDITIONThe filtrate was poured into cold 1N hydrochloric acid solution (40 ml)
7. 7
   Otherthe layers were separated
8. 8
   DryingThe organic layer was dried (magnesium sulfate)
9. 9
   Filtrationfiltered
10. 10
    Otherleaving an oil which
11. 11
    Otherwas purified by chromatography on silica gel
12. 12
    Washeluting with 10-30% ethyl acetate in hexane
13. 13
    Otherto give 730 mg

Procedure

A solution of (3R-cis)-tetrahydro-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepin-5(4H)-one (1.16 g., 3.25 mmol) [prepared as described by Yanagisawa et al., J. Med. Chem., Vol. 30, p. 1984-1991 (1987)] in distilled tetrahydrofuran (30 ml.), under an atmosphere of argon, was cooled to 0° C. and treated with powdered potassium hydroxide (540 mg., 10 mmol) and tetrabutylammonium bromide (97 mg, 0.3 mmol). Ethyl bromoacetate (501 mg., 3 mmol) was added dropwise with stirring. The mixture was stirred cold for two hours and then additional ethyl bromoacetate (501 mg., 3 mmol) was added. The mixture was stirred cold for an additional two hours and then diluted with ethyl acetate (50 ml) and anhydrous magnesium sulfate was added. The reaction mixture was filtered through a magnesium sulfate pad and the pad was washed several times with ethyl acetate. The filtrate was poured into cold 1N hydrochloric acid solution (40 ml) and the layers were separated. The organic layer was dried (magnesium sulfate), filtered and freed of solvent in vacuo leaving an oil which was purified by chromatography on silica gel, eluting with 10-30% ethyl acetate in hexane to give 730 mg. of product; Rf =0.32 (ethyl acetate:hexanes, 1:2).

Source