Hydrochloric Acid → HCID 178488293, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3,3-dimethylbutyraldehyde (Aldrich) (5 mL, 39.8 mmol) and Example 278A (641.0 mg, 4.0 mmol) was added a mixture of dimethylsulfoxide (560 μL, 8 mmol) and 12 N aqueous HCl (667 μL, 8 mmol). The reaction mixture was heated at 40° C. overnight. The mixture was concentrated and the residue was dried under vacuum for 2 hours. The residue (252 mg 0.9 mmol) was dissolved in tetrahydrofuran (10 mL). To this solution was added 5-bromo-2-methoxy-benzoic acid (209.0 mg, 0.9 mmol), N-(3-dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (73 mg, 0.9 mmol), 1-hydroxybenzotriazole (122.0 mg, 0.9 mmol) and triethylamine (315.0 μL, 2.3 mmol). The mixture was stirred overnight at 80° C., and cooled to room temperature. The mixture was diluted with ethyl acetate, washed with 1 M aqueous NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography using an Analogix® Intelliflash280™ (SiO2, 0-75% ethyl acetate in hexanes) to afford the title compound. 1H NMR (300 MHz, dimethylsulfoxide-d6) δ 1.32 (s, 9H), 1.58-1.71 (m, 1H), 1.75-1.86 (m, 2H), 1.87-2.00 (m, 1H), 3.64 (dd, J=15, 6.8 Hz, 1H), 3.78 (s, 3H), 3.79-3.83 (m, 1H), 4.19 (d, J=5.8 Hz, 2H), 4.23-4.35 (m, 1H), 7.05 (d, J=8.8 Hz, 1H), 7.25 (s, 1H), 7.56 (dd, J=8.8, 2.7 Hz, 1H), 7.76 (d, J=2.7 Hz, 1H.

Provenance & Evidence