Sodium hydride → Ammonium Acetate

Participants

Reaction Steps

A mixture of Example 200C (120 mg, 0.32 mmol), 2-(bromomethyl)tetrahydro-2H-pyran (62 mg, 0.35 mmol) and sodium hydride (60% dispersion in oil) (16 mg, 0.38 mmol) in tetrahydrofuran/N,N-dimethylformamide (2:1) (1 mL) was heated at 150° C. in a microwave (Emrys Personal Chemistry) for 30 minutes. The mixture was diluted with water, and extracted with ethyl acetate. The organic extract was dried (Na2SO4), filtered and concentrated. Purification by preparative high pressure liquid chromotography on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile: ammonium acetate (10 mM) over 15 minutes at a flow rate of 70 mL/minutes afforded the title compound. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm 1.17-1.30 (m, 1H) 1.40-1.51 (m, 3H) 1.60 (d, J=13.50 Hz, 1H) 1.64-1.76 (m, 7H) 1.76-1.83 (m, 1H) 1.85-1.89 (m, 6H) 1.96-2.03 (m, 3H) 3.74-3.83 (m, 1H) 3.88 (d, J=11.66 Hz, 1H) 4.18-4.28 (m, 2H) 7.20 (td, J=7.98, 2.76, 2.15 Hz, 1H) 7.38-7.45 (m, 1H) 7.66 (td, J=6.14 Hz, 1H) 7.80 (s, 1H); MS (ESI) m/z 473 (M+H)+.

Provenance & Evidence