反応 #1284

反応方程式

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

溶媒

ethyl acetate

—

hexanes

tetrahydrofuran

ethyl acetate

magnesium sulfate

反応条件

後処理

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
   ろ過The reaction mixture was filtered through a magnesium sulfate pad
5. 5
   洗浄the 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
   その他the layers were separated
8. 8
   乾燥The organic layer was dried (magnesium sulfate)
9. 9
   ろ過filtered
10. 10
    その他leaving an oil which
11. 11
    その他was purified by chromatography on silica gel
12. 12
    洗浄eluting with 10-30% ethyl acetate in hexane
13. 13
    その他to give 730 mg

実験手順

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).

出典