Acetic Acid → 4-(1,4-Dioxaspiro[4.5]dec-8-yl)hexahydro-1,4-oxazepine

Participants

Reaction Steps

Et3N (96.9 mL, 0.695 mol) was added in one portion to a stirred suspension of homomorpholine hydrochloride (79.76 g, 0.579 mol) and ketone 1 (90.5 g, 0.579 mol) in 1,2-dichloroethane (1.81 L). Then glacial acetic acid (34.8 mL, 0.607 mol) was added in one portion followed by solid NaBH(OAc)3 (154 g, 0.727 mol) in one portion as well. This was accompanied by 5° C. increase in the temperature of the reaction mixture. After 2 h 45 min the reaction was quenched by addition of 10% aqueous NaOH (800 mL). The mixture was stirred for 10 min. The organic layer was separated, washed with brine (100 mL), dried (MgSO4) and concentrated to afford an oil (142.36 g) with some suspended solid, which was filtered off (3.00 g). The aqueous part of the reaction mixture was combined with the brine washings and extracted with AcOEt (4×500 mL). Combined extracts were washed with brine (100 mL), dried (MgSO4) and concentrated to afford additional portion of oil (16.82 g). The two oily products were combined and distilled in vacuum to give 3 (101.07 g, 72%) as colorless liquid, b.p. 122° C./8.9·10−3 mbar. 1H NMR (400 MHz, CDCl3) δ 1.48-1.64 (m, 4H), 1.70-1.88 (m, 6H), 2.50-2.63 (m, 1H), 2.71-2.81 (m, 4H), 3.66-3.72 (m, 2H), 3.78 (t, J=6.0 Hz, 2H), 3.93 (s, 4H).

Provenance & Evidence