Acetic Acid → 1-methyl-4-(1,4-dioxaspiro[4.5]decan-8-yl)piperazine

Participants

Reaction Steps

1-Methyl-piperazine (128.27 g, 105.90 ml, 1.28 mol) was added in one portion to a stirred and cooled (3° C.) solution of 1,4-dioxaspiro[4.5]decan-8-one (200.00 g, 1.28 mol) in 1,2-dichloroethane (2.0 L). Then glacial acetic acid (76.90 g, 73.31 ml, 1.28 mol) was added in one portion followed by solid NaBH(OAc)3 (379.97 g, 1.79 mol) portionwise over 20 min. The reaction was slowly allowed to warm to RT and was stirred overnight. The reaction was quenched by addition of 10% aqueous NaOH (3×450 mL) with stirring over a period of 25 min. An exotherm of ca. 10° C. was observed. The mixture was stirred for 30 min. The organic layer was separated. Aqueous layer was further extracted with CH2Cl2 (3×1 L). Brine (1000 mL) was added to the aqueous layer and extracted with EtOAc (2×1000 mL). The combined organic solutions were dried (MgSO4) and concentrated to afford 9 (305.00 g, 1.27 mol, 99.10% yield) as brown/orange oil. 1H NMR (400 MHz, CDCl3) δ 1.45-1.68 (m, 4H), 1.72-1.90 (m, 4H), 1.99 (s, 3H), 2.45 (s, 2H), 2.56-2.67 (m, 1H), 2.87 (bs, 6H), 3.86-3.95 (m, 4H).

Provenance & Evidence