Hydrochloric Acid → Methyl 4-Boc-piperazine-2-acetate

Participants

Reaction Steps

The product of example 22A (9.78 g, 28.9 mmol) was combined with 20% Pd(OH)2—C (wet, 1.96 g) in methanol (100 mL) and 12 M aqueous HCl (2.9 mL, 35 mmol). The mixture was stirred under hydrogen (30 psi) at room temperature for 22 hours, then filtered and concentrated under vacuum. The residue was combined with 20% aqueous K2CO3 (40 mL) and ethyl acetate (50 mL), and the mixture stirred with ice-cooling as 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile (Aldrich, 7.12 g, 28.9 mmol) was added gradually over 5 minutes. The mixture was stirred with ice cooling for 1 hour, then it was allowed to warm to room temperature for 2 hours. The mixture was extracted with ethyl acetate (2×100 mL) and the combined ethyl acetate washes were extracted with 10% aqueous HCl (40 mL). The aqueous layer was washed with ethyl acetate (30 mL), then made basic (pH˜9) by gradual addition of solid K2CO3 (11.8 g). Ethyl acetate (80 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The aqueous phase was separated, and the organic phase was washed with brine (50 mL), dried (MgSO4) and concentrated under vacuum to leave the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 1.46 (s, 9H), 2.31-2.49 (m, 2H), 2.50-2.68 (m, 1H), 2.72-2.81 (m, 1H), 2.82-2.98 (m, 2H), 2.98-3.09 (m, 1H), 3.70 (s, 3H), 3.90 (d, J=9.9 Hz, 2H); MS (DCI) m/z 259 (M+H)+.

Provenance & Evidence