2-methyl-2-(4-oxocyclohexyl)propanoic acid synthesis

Yield:1447942-64-4 184 mg

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in chlorobenzene;acetonitrile at 20;

Steps:

To a solution of 2-methyl-2-(4-oxocyclohexyl)propanoic acid (0.184 g, 1 mmol) and DIPEA (0.192 mL, 1.100 mmol) in acetonitrile (1 mL) and CHCl₃ (1 mL) was added benzyl bromide (0.131 mL, 1.100 mmol) and the mixture was stirred at rt overnight. The reaction mixture was evaporated to dryness and purified by silica gel FCC (0-5% EtOAC in DCM) to afford benzyl 2-methyl-2-(4-oxocyclohexyl)propanoate as a clear oil (184 mg), which was dissolved in CH₂Cl₂ (2 mL) was treated with Deoxo-Fluor (0.442 mL, 2.40 mmol), followed by the addition of EtOH (5.8 mL). The resulting yellowish solution was stirred at rt overnight. The reaction mixture was diluted with sat. NaHCO₃ and EtOAc. The organic phase was separated and washed with water, sat. NaCl, dried over anhydrous MgSO₄, filtered and dried to yield a yellow oil. The crude product was purified by silica gel FCC (1:1 hexane-DCM) to afford benzyl 2-(4,4-difluorocyclohexyl)-2-methylpropanoate as a clear oil (143 mg) which was hydrogenated (0.053 g of 10% Pd-C, EtOAc) under balloon pressure for 4 h. The suspension was filtered and evaporated to dryness to afford Cap P-21. ¹H NMR (500 MHz, CDCl₃) δ ppm 2.08-2.23 (2H, m), 1.64-1.85 (5H, m), 1.36-1.54 (2H, m), 1.12-1.29 (6H, m).

References:

US2013/183269,2013,A1 Location in patent:Paragraph 1359; 1360