3,5-Dibromopyridine → Tert-butyl 2-[(5-bromopyridin-3-yl)amino]-3-methylbutanoate

Participants

Reaction Conditions

Reaction Steps

To a nitrogen degassed mixture of 3,5-dibromopyridine (5.0 g, 21.11 mmol), D-Valine t-butylester HCl (Aldrich Chemical, 4.43 g, 21.11 mmol) and sodium tert-butoxide (6.09 g, 63.3 mmol), in Toluene (200 ml) was added BINAP (2.63 g, 4.22 mmol) followed by tris(dibenzylideneacetone)-dipalladium(0) (Strem Chemical, 1.933 g, 2.111 mmol). The reaction was sealed and heated at 90° C. for 1 hr. The reaction was cooled, quenched into brine (100 mL), aqueous KHSO4 (20 mL) and ethyl acetate (200 mL). Aqueous sodium bicarbonate was added to adjust the pH to 8.0 and the organic layer removed. The aqueous layer was washed with ethyl acetate (100 mL). The combined organic extracts were washed with brine (100 mL), dried over sodium sulfate, filtered thru a pad of silica and the filtrate concentrated to oil. The oil was chromatographed on silica eluting with 5-30% ethyl acetate/hex to give 4.8 gm of compound I-2a, 69%.

Provenance & Evidence