반응 #67733

반응 방정식

triethylamine

tert-butyl 3-(2-amino-5-methylpyridin-4-yl)benzoate

1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid

Thionyl chloride

→

product

수율 70.3%

tert-Butyl 3-(2-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-5-methylpyridin-4-yl)benzoate

수율 70.3%

용매

dichloromethane

N,N-dimethylformamide

반응 조건

후처리

1. 1
   기타The excess thionyl chloride was removed under vacuum
2. 2
   workup.STIRRINGto stir for 15 hours at room temperature
3. 3
   기타The crude product was evaporated to dryness
4. 4
   기타purified on 12 g of silica gel utilizing a gradient of 0-40% ethyl acetate in hexanes

실험 절차

1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxylic acid (144 mg, 0.593 mmol) was placed in an oven-dried flask under nitrogen. Thionyl chloride (1 mL) and N,N-dimethylformamide (0.1 mL) were added and the solution was allowed to stir for 30 minutes at room temperature. The excess thionyl chloride was removed under vacuum and the resulting solid was suspended in 2 mL of anhydrous dichloromethane. This solution was then slowly added to a solution of tert-butyl 3-(2-amino-5-methylpyridin-4-yl)benzoate (129 mg, 0.454 mmol) in 5 mL of anhydrous dichloromethane containing triethylamine (0.165 mL, 1.19 mmol). The resulting mixture was allowed to stir for 15 hours at room temperature. The crude product was evaporated to dryness and then purified on 12 g of silica gel utilizing a gradient of 0-40% ethyl acetate in hexanes to yield the pure product as a yellow solid (162 mg, 0.319 mmol, 70.3%). ESI-MS m/z calc. 508.2. found; 509.1 (M+1)+ Retention time 2.22 minutes. 1H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.18 (s, 1H), 7.98-7.96 (m, 1H), 7.89 (s, 1H), 7.82 (d, J=1.6 Hz, 1H), 7.64-7.62 (m, 2H), 7.57 (d, J=1.6 Hz, 1H), 7.42 (d, J=8.3 Hz, 1H), 7.34 (dd, J=1.7, 8.3 Hz, 1H), 2.14 (s, 3H), 1.55 (s, 9H), 1.51-1.49 (m, 2H) 1.19-1.15 (m, 2H).

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