N-Methoxy-N-methylacetamide → HCID 18455601, compound

Participants

Reaction Conditions

Reaction Steps

t-Butyl lithium in hexanes (3.8 ml of a 1.7 M solution, 14.5 mmol) is added to THF at −78° C. in a flame dried round-bottomed flask. 4-[4-Bromo-2-(1,3-dioxolan-2-yl)phenyl]-2,6-dimethylmorpholine (from Step 2) (1.0 g, 2.9 mmol) is dissolved in THF (5 mL) and is slowly added to the t-BuLi solution over 7 minutes keeping the temperature below −70° C. The mixture is stirred for 30 minutes and N-methoxy-N-methyl-acetamide (0.34 mL, 3.2 mmol) is slowly added dropwise. The reaction is stirred at −78° C. for 30 minutes and then stored at 0° C. overnight. The reaction is quenched with 1 M HCl (22.5 mL) and then heated at 65° C. for 1 hour. The mixture is basified with 1 M aqueous Na2CO3 and extracted with EtOAc (2×). The combined organic layers are washed with brine, dried (Na2SO4) and concentrated. The resulting residue is adsorbed onto silica gel and purified by silica gel chromatography using 15-20% EtOAc in heptane as the eluent to afford 0.35 g (45%) a clear oil. 1H NMR (400 MHz, CDCl3) δ 10.1, 8.35, 8.12, 7.08, 3.93, 3.25, 2.76, 2.60, 1.25.

Provenance & Evidence