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

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).

1. stirringThe mixture was stirred cold for two hours
2. stirringThe mixture was stirred cold for an additional two hours
3. additionwas added
4. filtrationThe reaction mixture was filtered through a magnesium sulfate pad
5. washthe pad was washed several times with ethyl acetate
6. additionThe filtrate was poured into cold 1N hydrochloric acid solution (40 ml)
7. customthe layers were separated
8. dry with materialThe organic layer was dried (magnesium sulfate)
9. filtrationfiltered
10. customleaving an oil which
11. customwas purified by chromatography on silica gel
12. washeluting with 10-30% ethyl acetate in hexane
13. customto give 730 mg

ORD-Eintrag

ord-34f0afde778d417c9ab448469c03bc23

Quelldatensatz

uspto-grants-1998_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05723457