4-(Diethoxymethyl)benzaldehyde → N-[[4-(Diethoxymethyl)phenyl]methyl]tetrahydropyran-4-amine

Participants

Reaction Steps

To a solution of tetrahydropyran-4-amine 1 (100 g, 988.7 mmol) in MeOH (3.922 L) was added 4-(diethoxymethyl)benzaldehyde (196.1 g, 941.6 mmol) over 2 min at RT. The reaction mixture was stirred at RT for 80 min, until the aldimine formation was complete (as seen by NMR). NaBH4 (44.49 g, 1.176 mol) was carefully added over 45 min, maintaining the temperature between 24° C. and 27° C. by mean of an ice bath. After 75 min at RT, the reaction has gone to completion. The reaction mixture was quenched with 1M NaOH (1 L). The reaction mixture was partitioned between brine (2.5 L) and TBDME (4 L then 2×1 L). The organic phase was washed with brine (500 mL) and concentrated in vacuo. The crude mixture was redissolved in DCM (2 L). The aqueous phase was separated, the organic phase was dried over MgSO4, filtered and concentrated in vacuo to give the title compound as a yellow oil (252.99 g, 91% Yield); 1H NMR (400 MHz, CDCl3) δ 1.26 (t, 6H), 1.43-1.52 (m, 2H), 1.85-1.89 (m, 2H), 3.40 (td, 2H), 3.53-3.66 (m, 4H), 3.85 (s, 2H), 4.00 (dt, 2H), 5.51 (s, 1H), 7.33 (d, 2H) and 7.45 d, 2H) ppm; MS (ES+) 293.9.

Provenance & Evidence