(-)-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 605730노트

반응식

HRID 605730 반응식
[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

참가 물질

5

반응물 2

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

생성물 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-carboxylate수율 8.1%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-01993bc83e2b4f33bef0a90a0a502de5
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915250B2

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