Hydrochloric Acid → HCID 57959865, compound

Participants

Reaction Conditions

Reaction Steps

Diisobutylaluminium hydride (50 mL of a 1M solution in toluene, 50 mmol) was added to a pre-cooled (−78° C.) solution of tert-butyl 3-{[methoxy(methyl)amino]-carbonyl}-2-azabicyclo[2.2.1]heptane-2-carboxylate (6.17 g, 21.7 mmol) in diethyl ether (80 mL). The mixture was stirred at −78° C. for 2 hours and then at 0° C. for 10 min. The reaction was poured into a mixture of 1N hydrochloric acid (180 mL), diethyl ether (150 mL) and hexane (150 mL) and stirred for 20 min. The organic layer was washed with brine, dried Na2SO4) and concentrated. The residue was treated with THF (90 mL), tert-butylsulphinamide (3.15 g, 26 mmol) and titanium ethoxide (9.1 mL, 43.4 mmol) and stirred at ambient temperature for 12 h. The mixture was treated with brine (120 mL) and ethyl acetate (150 mL) and stirred for 30 min. The organic phase was removed and retained. The aqueous residue was washed with 2 further portions of ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified on a pad of silica gel eluting with iso-hexane containing 0.5% triethylamine on a gradient of ethyl acetate (0-40%) to give the title product (6.1 g, 85%). 1H NMR (400 MHz, CDCl3): δ 7.94-7.88 (1H, m), 4.33 (0.5H, s), 4.22 (0.5H, s), 4.10 (0.5H, m), 4.02 (0.5H, m), 2.75-2.65 (1.5H, m), 2.58 (0.5H, d, J=5.5), 1.88-1.50 (4H, m), 1.48-1.38 (9H, m), 1.34-1.26 (2H, m), 1.24-1.20 (9H, m).

Provenance & Evidence