Dichloromethane → HCID 20517541, compound

Participants

Reaction Conditions

Reaction Steps

2-Bromopropionylbromide (28.7 g, 0.13 mole) in dichloromethane (100 ml) was added dropwise with stirring to a solution of (3-methoxy)-2-methyl-2-[(methylamino)methyl]benzene methanol (25.9 g, 0.13 mol) and triethylamine (13.5 g) in dichloromethane (200 ml) keeping the temperature of the reaction between 10°-15° C. by ice-cooling. After 2 hours the reaction was washed with water, dilute hydrochloric acid and brine, dried (MgSO4) and evaporated to an oil (46.9 g). The last traces of dichloromethane were removed from the oil by evaporation with toluene. The oil was dissolved in dry toluene (200 ml) and added dropwise to a stirred suspension of sodium hydride (9.6 g, 0.2 mole of a 50% dispersion in oil pre-washed with ether) in dry dimethylformamide (200 ml) under nitrogen. The exothermic reaction which took place was kept at 35° C. by adjusting the rate of addition. When the addition was completed the reaction mixture was heated to 85° C. for 20 min. The reaction mixture was cooled and cautiously added to ice water (300 ml). The mixture was extracted with toluene and the organic extracts washed with dilute hydrochloric acid then brine. After drying (MgSO4) the solvent was removed to leave an oil which was distilled affording the title compound (25.8 g) as a colourless oil, bp 148°-149° at 0.7 mbar. Glc showed that the product was a mixture of diastereoisomers containing isomer A (apparently 2R*6R* configuration) 65% and isomer B (apparently 2R*6S* configuration) 35% by glc.

Provenance & Evidence