Triethylamine → Dimethylhydroxylamine

Participants

Reaction Steps

1.85 g of (4R)-1-(tert-butoxycarbonyl)-4-hydroxy-L-proline are dissolved in 80 ml of dichloromethane at 0° C. under N2. 3.72 ml of triethylamine and 1.97 ml of tert-butyl chloroformate are added. The reaction medium is stirred at ambient temperature for 1 h. In parallel, a solution of dimethylhydroxylamine is prepared by adding 1.86 ml of triethylamine to a solution of 1.56 g of dimethyl-hydroxylamine hydrochloride in dichloromethane, and then by filtering off the triethylamine hydrochloride. This second solution is added gently, at 0° C., to the first. The reaction medium is stirred at ambient temperature for 16 h. After hydrolysis with a 0.5N aqueous hydrochloric acid solution, extraction is carried out with dichloromethane until the aqueous phase is completely depleted. The organic phase is dried over MgSO4 and concentrated to dryness. 0.9 g of tert-butyl (2S,4R)-4-hydroxy-2-{[methoxy(methyl)amino]-carbonyl}pyrrolidine-1-carboxylate is obtained, which product is subsequently used as it is.

Provenance & Evidence