Hydrochloric Acid → Methyl {1-[(2R)-2-{[(4-fluorophenyl)sulfonyl](methyl)amino}-4-hydroxybutyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}acetate

Participants

Reaction Steps

To a stirred solution of NaHMDS (177.22 g, 966 mmol) in DMF (600 ml) at −10° C. was added a solution of methyl 1H-pyrrolo[2,3-b]pyridin-3-ylacetate (197.98 g, 969 mmol) in DMF (1000 ml) over 15 min., and stirring continue at that temperature for 2 hours. To the anion was added a solution of (2R)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1-[(4-fluoro-phenyl)sulfonyl]aziridine (288 g, 801 mmol) in DMF (1000 ml) over 1 hour. The reaction mixture was stirred for 1 hour at −10° C. Iodomethane (125.0 ml, 1999 mmol) was added at −10° C. and the reaction was stirred for 1.5 hour. Another aliquot of iodomethane (20 mL) was then added and the reaction was stirred for 30 more minutes. 3N HCl (1800 ml, 5400 mmol) was added slowly at −10° C. and the reaction was stirred for an additional hour. The reaction was quenched by pouring into saturated sodium bicarbonate solution (4 L) and ethyl acetate (4 L). The pH was still acidic so additional solid sodium bicarbonate was added. The layers were separated and the organic layer washed with ½ brine (1×4 L) and (1×2 L).

Provenance & Evidence