반응 #160393

반응 방정식

diisopropyl amine

n-BuMgCl

3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester

Iodine

→

5-iodo-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester

수율 99.1%

용매

THF

THF

THF

반응 조건

후처리

1. 1
   workup.STIRRINGstirred for 1 h at room temperature
2. 2
   workup.STIRRINGstirred for 1 h
3. 3
   기타Reaction mixture
4. 4
   기타was then quenched with 10% aq Na2S2O3 solution
5. 5
   추출extracted with EtOAc
6. 6
   세척washed with brine
7. 7
   기타dried
8. 8
   농축concentrated
9. 9
   기타Purification of the residue on small plug of silica gel bond
10. 10
    세척elute

실험 절차

To a stirred solution of diisopropyl amine (0.3 mL, 2.14 mmol) in THF (10 mL) was added n-BuMgCl (2.0 M in ether, 1.0 mL, 2.0 mmol), stirred for 24 h. To the resultant solution was added drop wise a solution of 3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (0.189 g, 0.5 mmol) in THF (2.0 mL), stirred for 1 h at room temperature. It was then added a solution of Iodine (1.28 g, 5.0 mmol) in THF (2.0 mL), stirred for 1 h. Reaction mixture was then quenched with 10% aq Na2S2O3 solution, extracted with EtOAc, washed with brine, dried, and concentrated. Purification of the residue on small plug of silica gel bond elute using DCM/CHCl3/MeOH/Et3N (200:90:16:1) as eluent gave 5-iodo-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (0.250 g, quantitative). NMR 1H (CDCl3, 400 MHz): 7.05 (s, 1H), 4.68-4.55 (m, 1H), 3.83 (s, 3H), 2.95-2.8 (m, 2H), 2.26 (s, 3H), 2.2-1.1 (m, 14H), 0.819 (d, J=6.3, 3H), 0.75-0.6 (m, 2H).

출처