Methyl iodide → HCID 66588570, compound

Participants

Reaction Steps

NaH (157 g, 1.5 eq, 60% containing in oil) was added into the solution of (1R,2S,3R,4R,5S,6R)-3,4,5-tris(benzyloxy)-2-(benzyloxymethyl)-6-(4-chloro-3-(4-ethylbenzyl)phenyl)cyclohexanol (4, R=Et, 2 g, 2.61 mmol) in anhydrous THF (10 mL) at 0° C. TBAI (0.1 eq) and CH3I (760 mg, 2 eq) were added into the reaction mixture after stirring for 1 h at the same temperature and the reaction mixture was stirred overnight at rt. Sat aq. NH4Cl was added to quench the reaction and the resulting mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and the filtrate was evaporated to dryness. The residue (yellow oil, 2.05 g) was dissolved in THF:CH3OH=2:1, treated with 1,2-dichlorobenzene (1% mol ratio) and Pd/C (10%, 1/1 weight ratio), and stirred over 2 h under H2 atmosphere at room temperature. The reaction was monitored by LC-MS until completion. The mixture was filtered, and the filtrate was evaporated to dryness and purified by preparative HPLC to give target compound 16 (987 mg, (white solid, yield of 90.0%). 1H-NMR (400 MHz, CD3COCD3): δ 7.32-7.34 (2H, m), 7.22 (1H, dd, J=2.4, 8.0 Hz), 7.12 (4H, dd, J=8.4 Hz), 4.15 (2H, s), 3.93-3.98 (1H, m), 3.70-.3.75 (1H,m), 3.65-3.67 (1H, m), 3.54-3.60 (2H, m), 3.37 (1H, t, J=10.4 Hz), 3.30 (1H, t, J=8.8 Hz), 2.84 (3H, s), 2.52-2.65 (3H, m), 1.51-1.58 (1H, m), 1.17 (3H, t, J=7.2 Hz); MS (ESI+): 421 [M+H]+, 438 [M+NH4]+, 841 [2M+H]+, 858 [2M+NH4]+, (ESI+): 465 [M+HCOO]−.

Provenance & Evidence