Acetic Acid → 3-[[3-(Methoxymethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 48035

Reaktionsgleichung

Reaktionsgleichung von HRID 48035
[CH3:1][O:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7].[F:11][C:12]([F:25])([O:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[CH:20]=O)[CH:13]([F:15])[F:14].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[F:44][C:45]([F:50])([F:49])[CH:46]1[O:48][CH2:47]1>ClC(Cl)C.C(#N)C.FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[CH3:1][O:2][CH2:3][C:4]1[CH:5]=[C:6]([N:7]([CH2:20][C:19]2[CH:22]=[CH:23][CH:24]=[C:17]([O:16][C:12]([F:25])([F:11])[CH:13]([F:15])[F:14])[CH:18]=2)[CH2:47][CH:46]([OH:48])[C:45]([F:50])([F:49])[F:44])[CH:8]=[CH:9][CH:10]=1

Komponenten

9

Edukt 5

HCID 176Acetic AcidHCID 118803Benzaldehyde, 3-(1,1,2,2-tetrafluoroethoxy)-HCID 5207692-(Trifluoromethyl)oxiraneHCID 5049666Sodium triacetoxyborohydrideHCID 130420323-(Methoxymethyl)aniline

Produkt 1

HCID 235060003-[[3-(Methoxymethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanolAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 2733225Ytterbium triflateKatalysatorHCID 6342AcetonitrileLösungsmittelHCID 63651,1-DichloroethaneLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  1. customquenched with aqueous saturated sodium bicarbonate
  2. additiondiluted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto give 4.27 g (12.4 mmol) of crude product
  7. temperaturethe stirred solution was warmed to 50° C. for 18 hours
  8. customThe reaction was quenched with water
  9. extractionextracted with ethyl acetate
  10. washThe organic layer was washed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-0885deb558664ed8afffd41b2288485f
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06699898B2

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