Imidazole → (2R,6S)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine

HRID 245351Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 245351
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[C:14]([F:15])=[C:13]([F:16])[CH:12]=[CH:11][C:10]=2[CH2:17][OH:18])[CH2:3]1.N1C=CN=C1.[C:24]([Si:28](Cl)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([CH3:27])([CH3:26])[CH3:25]>C(Cl)Cl>[Si:28]([O:18][CH2:17][C:10]1[C:9]([N:4]2[CH2:3][C@H:2]([CH3:1])[O:7][C@H:6]([CH3:8])[CH2:5]2)=[C:14]([F:15])[C:13]([F:16])=[CH:12][CH:11]=1)([C:24]([CH3:27])([CH3:26])[CH3:25])([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Komponenten

5

Edukt 3

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 67376655[2-((2R,6S)-2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-phenyl]-methanol2×

Produkt 1

HCID 67357593(2R,6S)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To an ice cooled and stirred solution of [2-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-phenyl]-methanol (Intermediate 2, 27.0 g, 105 mmol) in CH2Cl2 was added imidazole (8.5 g, 126 mmol) followed by t-butyl chlorodiphenylsilane (30 mL, 115 mmol) over a period of 15 min. The mixture was brought to room temperature and stirred for 12 h during which tlc showed the disappearance of starting material. The reaction mixture diluted with CH2Cl2 and washed successively with 1 N HCl (1×250 mL), water and brine. The organic layer dried (Na2SO4), filtered and concentrated. The residue was purified over a silica gel flash column using a gradient of ethyl acetate in pet. ether to give the title compound as a white solid. Yield: 45 g (94%).

Aufarbeitung

  1. customwas brought to room temperature
  2. washwashed successively with 1 N HCl (1×250 mL), water and brine
  3. dry with materialThe organic layer dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified over a silica gel flash column

Quellen und Nachweise

ORD-Eintrag
ord-8c490815bfd94f7d84fe0c0d50ed4f01
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658641B2

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