tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate → 4-[3-(Tert-butyl-dimethyl-silanyloxy)benzoyl]-piperidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

To the solution of (3-bromophenoxy)-tert-butyldimethylsilane (from Example 5, 6.12 g) in THF (120 mL) at −75° C. was slowly added nBuLi (9.37 mL of 2.5 M solution) under nitrogen. After 15 minutes, the solution of 4-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylic acid tert-butyl ester (5.80 g) in THF (10 mL) was dropwise added. The reaction was stirred under nitrogen overnight while it warmed to room temperature. The reaction was quenched by slow addition of aqueous NH4Cl solution (80 mL). The resulting mixture was extracted by EtOAc (120 mL). The organic layer was washed by water (80 mL×3) and brine (80 mL×1), dried by Na2SO4 and concentrated to give crude product (9.13 g), which was purified to afford pure 4-[3-(tert-butyl-dimethylsilanyloxy)benzoyl]piperidine-1-carboxylic acid tert-butyl ester (5.12 g; 57%). 1H NMR (600 MHz, DMSO-d6) δ 7.60 (d, 1H, J=8.0 Hz), 7.41 (dd, 1H, J=8.0, 8.0 Hz), 7.32 (m, 1H), 7.11 (dd, 1H, J=8.0, 2.5 Hz), 3.94 (m, 2H), 3.57 (m, 1H), 2.90 (bs, 2H), 1.72 (m, 2H), 1.38 (s, 9H), 1.37 (m, 2H), 0.94 (s, 9H), 0.19 (s, 6H).

Provenance & Evidence