(-)-alpha-Methoxy-alpha-(trifluoromethyl)phenylacetyl chloride → 1,1-dimethylethyl (2R)-2-(1-{[(phenylmethyl)oxy]carbonyl}-3-{[(2R)-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanoyl]oxy}azetidin-3-yl)piperidine-1-carboxylate

HRID 605730Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 605730
[OH:1][C:2]1([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][N:17]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:5][N:4]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH2:3]1.[CH3:29][O:30][C@:31]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([C:35]([F:38])([F:37])[F:36])[C:32](Cl)=[O:33]>ClCCl.CN(C1C=CN=CC=1)C>[C:10]1([CH2:9][O:8][C:6]([N:4]2[CH2:3][C:2]([C@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][N:17]3[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])([O:1][C:32](=[O:33])[C@:31]([O:30][CH3:29])([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:35]([F:37])([F:38])[F:36])[CH2:5]2)=[O:7])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Komponenten

5

Edukt 2

HCID 3080792(-)-alpha-Methoxy-alpha-(trifluoromethyl)phenylacetyl chlorideHCID 59469243tert-Butyl 2-(1-((benzyloxy)carbonyl)-3-hydroxyazetidin-3-yl)piperidine-1-carboxylate

Produkt 1

HCID 670515881,1-dimethylethyl (2R)-2-(1-{[(phenylmethyl)oxy]carbonyl}-3-{[(2R)-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanoyl]oxy}azetidin-3-yl)piperidine-1-carboxylateAusbeute 8,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 1,1-dimethylethyl 2-(3-hydroxy-1-{[(phenylmethyl)oxy]carbonyl}azetidin-3-yl)piperidine-1-carboxylate (368 mg, 0.94 mmol), prepared using procedures similar to those described in Reference 5, in dichloromethane (5 mL) was added DMAP (115 mg, 0.94 mmol) and the resulting solution was cooled to 0° C. (R)-(−)-α-Methoxy-α-trifluoromethylphenylacetyl chloride (105 μL, 0.56 mmol) was added to the solution by syringe and the mixture was allowed to warm to room temperature then stirred an additional 12 hours. The solution was then partitioned with saturated aqueous sodium bicarbonate and the organic phase dried over anhydrous magnesium sulfate then filtered and concentrated to an oily residue. Silica gel flash chromatography using hexanes:ethyl acetate 3:1 as eluent afforded the less polar 1,1-dimethylethyl(2R)-2-(1-{[(phenylmethyl)oxy]carbonyl}-3-{[(2R)-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanoyl]oxy}azetidin-3-yl)piperidine-1-carboxylate (27.5 mg, 5% yield), the more polar 1,1-dimethylethyl(2S)-2-(1-{[(phenylmethyl)oxy]carbonyl}-3-{[(2R)-3,3,3-trifluoro-2-(methyloxy)-2-phenylpropanoyl]oxy}azetidin-3-yl)piperidine-1-carboxylate (105 mg, 19% yield) and starting material (253 mg, 69% recovery).

Aufarbeitung

  1. additionwas added to the solution by syringe
  2. customThe solution was then partitioned with saturated aqueous sodium bicarbonate
  3. dry with materialthe organic phase dried over anhydrous magnesium sulfate
  4. filtrationthen filtered
  5. concentrationconcentrated to an oily residue

Quellen und Nachweise

ORD-Eintrag
ord-01993bc83e2b4f33bef0a90a0a502de5
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07915250B2

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