Sodium borohydride → 4-Benzyl-2,2,6,6-tetramethylmorpholine

Participants

Reaction Conditions

Reaction Steps

Add solid NaBH4 (776 mg, 20.5 mmol) to a solution of 4-benzyl-2-iodomethyl-2,6,6-trimethyl-morpholine (6.22 g, 17.3 mmol) in DMSO (20 mL) and then heat the mixture at 100° C. After 2 h, add additional DMSO (10 mL). After an additional 1.25 h, add extra NaBH4 (120 mg, 3.17 mmol). Remove the heat after an additional 1.25 h (total reaction time=4.5 h). Quench the excess NaBH4 with 5 M HCl (20 ml). After 15 min, add 5 M NaOH (20 mL) and 1 M Na2S2O3 (20 mL) and then stir the mixture overnight. Dilute the mixture with tert-butyl methyl ether (250 mL) and water (100 mL). Separate the organic solution and wash with additional water (4×100 mL). Dry, filter and concentrate the organic solution. Purify the residue by flash chromatography, using a gradient from 50% to 100% CH2Cl2 in pentane as eluent. Dry the product so obtained briefly at 60° C. under vacuum to give the title compound (2.43 g, 60%) as a colorless liquid. 1H NMR (400 MHz, DMSO-d6): δ 7.2-7.4 (5H, m), 3.45 (2H, s), 2.12 (4H, s), 1.15 (12H, s).

Provenance & Evidence