反应详情

温度

5 °C

The 1M solution of trans-4-methylcyclohexyl carboxylic acid chloride was added to a solution of 5-bromo-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester (24.79 g, 65 mmol) in toluene (25 ml) followed by pyridine (5.78 ml, 71.5 mmol). The resulting mixture was then stirred for 16 h at reflux. The reaction mixture was diluted with toluene (60 ml) and cooled down to 5° C. After the addition of pyridine (12 ml) and MeOH (5.6 ml), the mixture was stirred 2 h at 5° C. The white suspension was filtered off and the toluene was added to the mother liquor. The organic phase was washed with 10% citric acid, aq. Sat NaHCO3, dried (Na2SO4) and concentrated. The residue was triturated in boiling hexane (1500 ml). The reaction mixture was allowed to cool down to room temperature. The reaction flask was immersed into ice bath, and stirred for 30 min; white solid was filtered off, and washed with cold hexane (225 ml). The solid was purified by silica gel column chromatography using 20% EtOAc:hexanes as eluent to furnished the final compound 5-Bromo-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (10.5 g, 32%). 1H NMR (CDCl3, 400 MHz): 6.84 (s, 1H), 4.62 (m, 1H), 3.90-3.82 (m, 4H), 3.80 (s, 3H), 1.92-1.81 (m, 2H), 1.77-1.11 (m, 14H), 1.79 (d, 3H), 0.77-0.59 (m, 2H).

1. temperatureat reflux
2. stirringthe mixture was stirred 2 h at 5° C
3. filtrationThe white suspension was filtered off
4. additionthe toluene was added to the mother liquor
5. washThe organic phase was washed with 10% citric acid, aq. Sat NaHCO3
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated
8. customThe residue was triturated
9. temperatureto cool down to room temperature
10. customThe reaction flask was immersed into ice bath
11. stirringstirred for 30 min
12. filtrationwhite solid was filtered off
13. washwashed with cold hexane (225 ml)
14. customThe solid was purified by silica gel column chromatography