Sodium Sulfite → Rotigotine

Participants

Reaction Steps

2.00 kg (9.74 mol) of (S)-5,6,7,8-tetrahydro-6-propylamino-1-naphthol, 4.12 kg (14.62 mol) of 2-(2-thienyl)ethyl 4-methylbenzenesulfonate (with a sulfonate/starting material mole ratio of 1.5/1), 3.69 kg (29.25 mol) of sodium sulfite (with a sodium sulfite/starting material mole ratio of 3.0/1) and 25 L of xylene were mixed to form a mixture, and the mixture was refluxed. After 48 hours, the reaction was stopped. The mixture was cooled to room temperature, and washed with an appropriate amount of water. Active carbon was added to decolorize the mixture. The mixture was filtered and left standing. An organic phase was reserved and concentrated under vacuum to obtain a residue. The residue was separated by silica gel column chromatography, and eluted with ethyl acetate and hexane (1:19), to obtain 1.64 kg of (S)-5,6,7,8-tetrahydro-6-[propyl[2-(2-thienyl)ethyl]amino]-1-naphthol, which was converted into a hydrochlorate thereof. The yield was 47.8%.

Provenance & Evidence