Hydrochloric Acid → HCID 57501750, compound

Participants

Reaction Conditions

Reaction Steps

Dissolve 2,2-dimethyl-propionic acid 4-{[4-(2-hydroxy-ethyl)-2-(4-methoxy-phenyl)-thiazole-5-carbonyl]-amino}-2-methoxy-phenyl ester (480 mg, 0.98 mmol) and NEt3 (177 mL, 1.27 mmol) in dry CH2Cl2 and cool to 0° C. Add dropwise methanesulfonyl chloride (98.1 mL, 1.27 mmol) and stir for 30 min. Quench the reaction mixture with saturated NH4Cl solution and extract with CH2Cl2 (3×10 mL). Dry, filter, and concentrate. Redissolve the crude material in dry DMF (6.5 mL) and chill to 0° C. Add portionwise NaH (60% dispersion, 51 mg, 1.27 mmol) then warm to ambient temperature overnight. Add 1N HCl (20 mL) and extract with EtOAc (3×10 mL). Collect insoluble solid from portioned layers via filtration. Wash the filtrate with water (40 mL), dry, filter, and concentrate. Combine the resulting material with the collected solid to give the title compound as a yellow solid (749 mg, 99%). MS (ES+) 467.3 (M+1)+. 1H NMR (400 MHz, CD3OD): δ 7.96 (d, 2H, J=8.4 Hz), 7.14 (d, 1H, J=2.2 Hz), 7.05 (d, 2H, J=8.4 Hz), 7.04 (dd, 1H, J=8.8, 2.2 Hz), 6.96 (dd, 1H, J=8.4, 2.2 Hz), 4.15 (t, 2H, J=7.0 Hz), 3.87 (s, 3H), 3.81 (s, 3H), 3.27 (t, 2H, J=7.5 Hz), 1.35 (s, 9H).

Provenance & Evidence