تفاعل #1104169

معادلة التفاعل

3-(methoxymethyl)aniline

3-(1,1,2,2-tetrafluoroethoxy)benzaldehyde

1,1,1-trifluoro-2,3-epoxypropane

acetic acid

NaBH(OAc)3

→

3-[[3-(methoxymethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]1,1,1-trifluoro-2-propanol

المردود 97.0%

المذيبات

dichloroethane

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىquenched with aqueous saturated sodium bicarbonate
2. 2
   workup.ADDITIONdiluted with ethyl acetate
3. 3
   غسيلThe organic layer was washed with brine
4. 4
   تجفيفdried over MgSO4
5. 5
   تركيزconcentrated in vacuo to (
6. 6
   أخرىgive 4.27 g (12.4 mmol) of crude product
7. 7
   درجة الحرارةthe stirred solution was warmed to 50° C. for 18 hours
8. 8
   أخرىThe reaction was quenched with water
9. 9
   استخلاصextracted with ethyl acetate
10. 10
    غسيلThe organic layer was washed with brine
11. 11
    تجفيفdried over MgSO4
12. 12
    تركيزconcentrated in vacuo

الإجراء التجريبي

EX-514C) The 3-(methoxymethyl)aniline (1.85 g, 13.51 mmol) product from EX-514B and 3-(1,1,2,2-tetrafluoroethoxy)benzaldehyde (3 g, 13.5 mmol) were dissolved in 25 mL of dichloroethane and acetic acid (0.85 mL, 14.8 mmol), then solid NaBH(OAc)3 (3.73 g, 17.6 mmol) was added. The mixture was stirred at room temperature for 48 hours, then quenched with aqueous saturated sodium bicarbonate and diluted with ethyl acetate. The organic layer was washed with brine, then dried over MgSO4, and concentrated in vacuo to (give 4.27 g (12.4 mmol) of crude product. The crude product and 1,1,1-trifluoro-2,3-epoxypropane (1.2 mL, 13.7 mmol) were dissolved in 20 mL of acetonitrile. Ytterbium (III) trifluoromethanesulfonate (0.77 g, 1.24 mmol) was added, and the stirred solution was warmed to 50° C. for 18 hours. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, then dried over MgSO4, and concentrated in vacuo to give 5.96 g (97%) of the desired 3-[[3-(methoxymethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]1,1,1-trifluoro-2-propanol product as a brown oil. The crude product was greater than 95% pure by reverse phase HPLC analysis and was used without further purification. HRMS calcd. for C20H21F7NO3: 456.1410 [M+H]+, found: 456.1409. 1H NMR (CDCl3) δ3.3 (s, 3H), 3.6 (dd, 1H), 3.9 (dd, 1H), 4.3 (m, 1H), 4.4 (s, 2H), 4.7 (m, 2H), 5.9 (tt, 1H), 6.6-6.8 (m, 3H), 7.1-7.2 (m, 4H), 7.3 (t, 1H).

المصدر