반응 #76313

ord-0885deb558664ed8afffd41b2288485f

반응 방정식

COCc1cccc(N)c1
3-(methoxymethyl)aniline
O=Cc1cccc(OC(F)(F)C(F)F)c1
3-(1,1,2,2-tetrafluoroethoxy)benzaldehyde
FC(F)(F)C1CO1
1,1,1-trifluoro-2,3-epoxypropane
CC(=O)O
acetic acid
CC(=O)O[BH-](OC(C)=O)OC(C)=O.[Na+]
NaBH(OAc)3
COCc1cccc(N(Cc2cccc(OC(F)(F)C(F)F)c2)CC(O)C(F)(F)F)c1
3-[[3-(methoxymethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol
수율 97.0%

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타quenched with aqueous saturated sodium bicarbonate
  2. 2
    workup.ADDITIONdiluted with ethyl acetate
  3. 3
    세척The organic layer was washed with brine
  4. 4
    건조dried over MgSO4
  5. 5
    농축concentrated in vacuo
  6. 6
    기타to give 4.27 g (12.4 mmol) of crude product
  7. 7
    온도the stirred solution was warmed to 50° C. for 18 hours
  8. 8
    기타The reaction was quenched with water
  9. 9
    추출extracted with ethyl acetate
  10. 10
    세척The organic layer was washed with brine
  11. 11
    건조dried over MgSO4
  12. 12
    농축concentrated in vacuo

실험 절차

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).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US06699898B2uspto-grants-2004_03