反应详情

Methyl 2-(3-bromophenoxy)-4-methylpentanoate, in a mixture of water (42 mL), methanol (8 mL) and tetrahydrofuran (4 mL) was treated with lithium hydroxyde monohydrate (1.3 g, 31.6 mmoles) until disappearance of the starting material was observed by TLC. The reaction was diluted with 1.2 N hydrochloric acid until pH 1. The aqueous phase was extracted 3 times with dichloromethane. The organic phase was concentrated under reduced pressure to provide a residue that was used as such in the next reaction. To a solution of the resulting crude 2-(3-bromophenoxy)-4-methylpentanoic acid in DMF (30 mL) was added aminoacetonitrile hydrochloride (2.9 g, 31.5 mmoles) and HATU (6.3 g, 16.5 mmoles). After stirring for 1 minute, triethylamine (8.75 mL, 63 mmoles) was added in one portion. The reaction was stirred overnight, diluted with ethyl acetate and water. The organic phase was separated and washed twice with 1.2 N hydrochloric acid, brine and dried over magnesium sulfate. After concentration under reduced pressure, the solid 2-(3-bromophenoxy)-N-(cyanomethyl)-4-methylpentanamide obtained was sufficiently pure.

1. extractionThe aqueous phase was extracted 3 times with dichloromethane
2. concentrationThe organic phase was concentrated under reduced pressure
3. customto provide a residue that
4. customsuch in the next reaction
5. stirringThe reaction was stirred overnight
6. customThe organic phase was separated
7. washwashed twice with 1.2 N hydrochloric acid, brine
8. dry with materialdried over magnesium sulfate
9. concentrationAfter concentration under reduced pressure