反应详情

A solution of oxalyl chloride (12.69 g, 0.10 mol) in dichloromethane (150 mL) was cooled to approximately −78° C. and treated dropwise under nitrogen with a solution of anhydrous dimethylsulfoxide (15.63 g, 0.20 mol) in dichloromethane (50 mL). 15 min after the addition was complete, a solution of ethyl 4-(hydroxymethyl)-piperidine-1-carboxylate (15.60 g, 83.3 mmol) (B2) in dichloromethane (50 mL) was added dropwise. 30 minutes after the addition was complete, a solution of triethylamine (25.30 g, 0.25 mol) in dichloromethane (50 mL) was added dropwise and the reaction warmed to room temperature. The reaction was stirred at room temperature for 1 hour, then quenched with saturated sodium bicarbonate (500 mL). The layers were separated and the aqueous layer extracted once with dichloromethane (200 mL). The pooled organic layers were washed with water (3×100 mL), saturated sodium bicarbonate (1×100 mL) and saturated brine (1×100 mL), then dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford ethyl 4-formylpiperidine-1-carboxylate (B3) as a viscous amber oil. 1H-NMR (400 MHz, CDCl3) δ 9.64 (s, 1H), 4.10 (q, J=7.2 Hz, 2H), 4.00 (br m, 2H), 2.97 (m, 2H), 2.40 (m, 1H), 1.87 (br m, 2H), 1.54 (m, 2H), 1.23 (t, J=7.0 Hz, 3H).

1. addition15 min after the addition
2. addition30 minutes after the addition
3. customquenched with saturated sodium bicarbonate (500 mL)
4. customThe layers were separated
5. extractionthe aqueous layer extracted once with dichloromethane (200 mL)
6. washThe pooled organic layers were washed with water (3×100 mL), saturated sodium bicarbonate (1×100 mL) and saturated brine (1×100 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationThe filtrate was concentrated in vacuo