反应详情

Dissolve (S)-2-(2-Isopropoxy-3-methylphenyl)-1-(4-piperidinyl)ethanol (21.5 g, 78 mmol), N-(2,2,-dimethoxyethyl)formamide (15.5 g, 117 mmol) and BF3□Et2O (66.1 g, 466 mmol) in CH2Cl2 (350 mL). Heat the solution to reflux for 3 hr and then allow to stand 15 hr at room temperature. Evaporate the solvent and dissolve the residue in CH2Cl2. Treat the resulting solution with 50% aqueous NaOH to obtain a pH of 13. Separate the phases and extract the aqueous phase with CH2Cl2. Combine the organic phases, wash with brine and dry over MgSO4. Evaporate the solvent to afford a residue. Purify the residue by chromatography over SiO2 using CHCl3:2M NH3/MeOH (8:2). Evaporate the product-containing fractions and triturate with 1:1 Et2O:heptane to afford a crystalline solid; 1H-NMR (CDCl3) δ 8.2, 7.9 (2s, 1H), 7.0-6.7 (m, 2H), 6.2 (m, 1H), 4.8 (m, 1H). 4.2 (m, 1H), 4.1 (m, 1H), 3.3 (m, 2H), 3.2 (m, 2H), 2.9 (m, 1H), 2.7, (m, 2H), 2.5 (m, 2H), 2.2 (s, 3H), 2.0-1.4 (m, 5H), 1.3-1.2 (2d, 6H).

1. temperatureHeat the solution
2. temperatureto reflux for 3 hr
3. customEvaporate the solvent
4. dissolutiondissolve the residue in CH2Cl2
5. additionTreat the resulting solution with 50% aqueous NaOH
6. customto obtain a pH of 13
7. customSeparate the phases
8. extractionextract the aqueous phase with CH2Cl2
9. washwash with brine
10. dry with materialdry over MgSO4
11. customEvaporate the solvent
12. customto afford a residue
13. customPurify the residue by chromatography over SiO2
14. customEvaporate the product-containing fractions
15. customtriturate with 1:1 Et2O
16. customheptane to afford a crystalline solid