Chlorotrimethylsilane → HCID 21180610, compound

Participants

Reaction Steps

A suspension of 4.38 g (67.0 mmol) of Zn powder in 40 mL of THF was treated with 0.58 mL (6.7 mmol) of 1,2-dibromoethane. The resulting mixture was heated at reflux for 2 min, then cooled to rt. Trimethylsilyl chloride (0.43 mL 3.4 mmol) was then added, the resulting mixture was stirred at ambient temperature for 20 min, the cooled to −5° C. A solution of 2.88 g (13.4 mmol) of 1-(t-butoxycarbonyl)-4-formyl piperidine and 9.52 g (46.9 mmol) of ethyl bromodifluoroacetate in 10 mL of THF was gradually added to the activated Zn. After the resulting exotherm subsided, the cooling bath was removed and the resulting mixture was stirred at rt for 20 h. The reaction was quenched with 50 mL of sat'd NH4Cl and the resulting mixture was partitioned between 300 mL of ether and 100 mL of H2O. The organic layer was separated, washed with 50 mL of sat'd NaHCO3, 50 mL of sat'd NaCl, dried and concentrated. Flash chromatography on 200 g of silica gel using 4:1 v/v, then 2:1 v/v hexanes/EtOAc as the eluants afforded 2.25 g (52%) of the title compound as an oil: 1H NMR (500 MHz, CDCl3) δ 1.31-1.34 (m, 1H), 1.37 (t, J=7.0, 3H), 1.45 (s, 9H), 1.69-1.72 (m, 2H), 1.86-1.92 (m, 2H), 2.40 (d, J=7.0, 1H), 2.68-2.72 (m, 2H), 3.83-3.90 (m, 1H), 4.104.20 (m, 2H), 4.36 (q, J=7.0, 2H).

Provenance & Evidence