2-Acetyl-5,6,7,8-tetrahydroquinoline-6-carboxylic acid → 2-(2-Hydroxypropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a 25 mL flask was added 2-acetyl-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (146 mg, 0.667 mmol) and tetrahydrofuran (2.7 mL). The system was purged with nitrogen and cooled to 0° C. 3M of methylmagnesium chloride in tetrahydrofuran (0.598 mL, 2.00 mmol) was added dropwise over 3 minutes. The mixture was stirred at 0° C. for 5 minutes then allowed to warm to room temperature. Additional THF (5 mL) was added and the mixture was sonicated for 1 minute to break up solids. After a total of 2 hours the reaction was carefully quenched by dropwise addition of 1M NaH2PO4 (10 mL). The mixture was diluted with DCM (10 mL) and citric acid (0.5 mL) was added to obtain a pH of 4. The layers were separated and the aqueous was extracted with 3:1 DCM/THF (10 mL) followed by with 3:1 CHCl3/IPA (15 mL×2), dried (Na2SO4), filtered and evaporated to obtain a reddish foam (160 mg, theoretical yield), which was used directly in the next step. m/z=236.2 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 7.55 (d, J=8.1 Hz, 1H), 7.39 (d, J=8.1 Hz, 1H), 3.10-2.90 (m, 4H), 2.85-2.74 (m, 1H), 2.32-2.25 (m, 1H), 2.06-1.95 (m, 1H), 1.51 (s, 6H).

Provenance & Evidence