反应详情

Into a flamed dried round bottom flask charged with n-dodecylamine (586 mg, 3.16 mmol) in 7 mL THF at −20° C. was added n-BuLi (1.8 mL, 3.6 mmol) as a solution in hexanes. After the addition, the reaction was warmed up to room temperature and stirred for one-half hour. Then the solution was cooled to −20° C. and was added to a solution of 3-bromo-4-(2-hydroxyethoxy)-5-(3-chloro-4-fluorophenyl)benzoic acid ethyl ester (400 mg, 0.957 mmol) in 8 mL THF that had been previously cooled to −40° C. The resulting mixture was stirred at −40° C. for 5 min after which point the reaction mixture was allowed to warm up to room temperature. The reaction was diluted with water and 2N HCl then extracted with EtOAc three times. The combined organic extracts were washed with sat NaHCO3 then dried over Na2SO4. After filtering and removal of solvent in vacuo, there yielded a yellow oil that was subjected to column chromatography on silica gel (10% EtOAc: 90% Hexanes followed by 25% EtOAc: 75% Hexanes). There resulted 300 mg, 58% of the amide as a yellow oil. 1H NMR (CDCl3) 0.868 (t, J=8.13 Hz, t); 1.20–1.40 (m, 18H); 1.48–1.67 (m, 2H); 1.895–2.00 (bs, 1H); 3.427 (q, J=8.13 Hz, 2H); 3.636–7.71 (m, 4H); 6.014 (m, 1H); 7.20–7.24 (m, 1H); 7.40–7.454 (m, 1H); 7.586–7.668 (m, 2H); 7.868 (d, J=2.04 Hz, 1H).

1. customInto a flamed dried round bottom flask
2. additionAfter the addition
3. temperatureThen the solution was cooled to −20° C.
4. temperaturehad been previously cooled to −40° C
5. stirringThe resulting mixture was stirred at −40° C. for 5 min after which
6. temperatureto warm up to room temperature
7. extractionthen extracted with EtOAc three times
8. washThe combined organic extracts were washed with sat NaHCO3
9. dry with materialthen dried over Na2SO4
10. filtrationAfter filtering
11. customremoval of solvent in vacuo, there
12. customyielded a yellow oil that