Hydrochloric Acid → HCID 178498040, compound

Participants

Reaction Steps

To a mixture of (cis)-4-((tert-butoxycarbonyl)amino)cyclohexyl methanesulfonate (5.36 mL, 22.93 mmol), methyl 5-chloro-3-hydroxy-2-methylbenzoate (4.0 g, 19.94 mmol), and cesium carbonate (9.74 g, 29.9 mmol) was added N,N-dimethylformamide (DMF) (100 mL). The suspension was stirred at RT for 15 min, then heated at 65° C. under nitrogen septum for 3 days. The reaction was allowed to cool to RT and was poured into ice/saturated NH4Cl (500 mL). The mixture was neutralized with 1 M HCl and extracted with 1:1 EtOAc/ether (2×). The combined organics were washed with brine, dried over magnesium sulfate, and concentrated. The resultant liquid was dried under high vacuum for 2 h. Purification of the residue by flash chromatography (200 gram Isco silica column, 4-50% ether/heptane) gave methyl 3-(((trans)-4-((tert -butoxycarbonyl)amino)cyclohexyl)oxy)-5-chloro-2-methylbenzoate (1.87 g, 4.70 mmol, 23.57% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.27-1.48 (m, 13 H) 1.80 (d, J=10.61Hz, 2 H) 1.98-2.07 (m, 2 H) 2.25 (s, 3 H) 3.23-3.33 (m, 1 H) 3.82 (s, 3 H) 4.30-4.45 (m, 1 H) 6.86 (d, J=7.58 Hz, 1 H) 7.28 (d, J=2.02 Hz, 1 H) 7.35 (d, J=2.02 Hz, 1 H). MS(ES) [M+H]+ 420.1 (Na adduct).

Provenance & Evidence