(3aR,5R,7aS)-5-[(Benzyloxy)methyl]-7a-(2,4-difluorophenyl)hexahydro-1H-pyrano[3,4-c][1,2]oxazole → [(2R,4R,5S)-5-amino-2-[(benzyloxy)methyl]-5-(2,4-difluorophenyl)tetrahydro-2H-pyran-4-yl]methanol

HRID 1427398Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1427398
[CH2:1]([O:8][CH2:9][C@@H:10]1[O:18][CH2:17][C@:13]2([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[NH:14][O:15][CH2:16][C@@H:12]2[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Zn].C(O)(=O)C>[NH2:14][C@@:13]1([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[CH2:17][O:18][C@@H:10]([CH2:9][O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:11][C@H:12]1[CH2:16][OH:15]

Komponenten

4

Edukt 1

HCID 71268780(3aR,5R,7aS)-5-[(Benzyloxy)methyl]-7a-(2,4-difluorophenyl)hexahydro-1H-pyrano[3,4-c][1,2]oxazole

Produkt 1

HCID 71277793[(2R,4R,5S)-5-amino-2-[(benzyloxy)methyl]-5-(2,4-difluorophenyl)tetrahydro-2H-pyran-4-yl]methanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23994ZincKatalysatorHCID 176Acetic AcidLösungsmittel

Versuchsvorschrift

(3aR,5R,7aS)-5-[(Benzyloxy)methyl]-7a-(2,4-difluorophenyl)hexahydro-1H-pyrano[3,4-c][1,2]oxazole (C21) (742 mg, 2.05 mmol) was mixed with acetic acid (6.8 mL). After addition of zinc powder (1.75 g, 26.7 mmol), the reaction mixture was stirred for 18 hours. Insoluble material was removed via filtration, and the solids were washed with ethyl acetate. The combined filtrates were washed with saturated aqueous sodium bicarbonate solution, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide the product as an opaque oil, which was used in the following reaction without additional purification. Yield: 748 mg, quantitative. LCMS m/z 364.4 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.65 (ddd, J=14.0, 4.3, 2.6 Hz, 1H), 1.98-2.16 (br m, 1H), 2.24-2.41 (br m, 1H), 3.32-3.41 (m, 1H), 3.42-3.60 (m, 3H), 3.60-3.73 (br m, 1H), 3.82-3.92 (br m, 1H), 4.22 (dd, J=11.5, 2.3 Hz, 1H), 4.61 (AB quartet, upfield signals are broadened, JAB=12.1 Hz, ΔνAB=29 Hz, 2H), 6.83 (ddd, J=12.6, 8.6, 2.6 Hz, 1H), 6.92-7.05 (br m, 1H), 7.27-7.40 (m, 5H), 7.62-7.79 (br m, 1H).

Aufarbeitung

  1. customInsoluble material was removed via filtration
  2. washthe solids were washed with ethyl acetate
  3. washThe combined filtrates were washed with saturated aqueous sodium bicarbonate solution
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-b3258742f53b4516b8a942fc91f24f27
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933221B2

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