Methanol → cis-4-[[3,5-Bis(trifluoromethyl)benzyl]oxy]-1-ethyl-3-phenylpiperidine oxalate

HRID 1437677노트

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HRID 1437677 반응식
[C:1]([N:4]1[CH2:9][CH2:8][C@H:7]([O:10][CH2:11][C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=2)[C@H:6]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:5]1)(=O)[CH3:2].CO.[C:34]([OH:39])(=[O:38])[C:35]([OH:37])=[O:36]>C1COCC1.B>[C:34]([OH:39])(=[O:38])[C:35]([OH:37])=[O:36].[F:25][C:22]([F:23])([F:24])[C:14]1[CH:13]=[C:12]([CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=1)[CH2:11][O:10][C@H:7]1[CH2:8][CH2:9][N:4]([CH2:1][CH3:2])[CH2:5][C@H:6]1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

참가 물질

6

반응물 3

HCID 887MethanolHCID 971Oxalic AcidHCID 86606806HCID 86606806, 화합물

생성물 1

HCID 86606828cis-4-[[3,5-Bis(trifluoromethyl)benzyl]oxy]-1-ethyl-3-phenylpiperidine oxalate수율 61%

시약·촉매·용매 2

HCID 6331Borane용매HCID 8028Tetrahydrofuran용매

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온도
80 °C

실험 절차

To a solution of the compound (0.88 g) obtained in Example 2 in THF (10 ml), 1 M borane and THF complex (10 ml) was added at 0° C., and the reaction mixture was stirred at 80° C. for 2 hours. The reaction mixture was cooled, and then methanol (2 ml) was added thereto, and concentrated under reduced pressure. To the obtained residue, 6 N hydrogen chloride (6 ml) and methanol (6 ml) were added, and the reaction mixture was stirred at 100° C. for 2 hours. The reaction mixture was cooled, and then made basic with an aqueous 12 N sodium hydroxide solution. The mixture was concentrated under reduced pressure, and then the product was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried, and then the solvent was evaporated under reduced pressure. The obtained residue was isolated and purified by silica gel column chromatography (acetone:methanol=20:1), and treated with 1 equivalent of oxalic acid to obtain the title compound as colorless crystals (0.52 g, 61%).

후처리

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. additionTo the obtained residue, 6 N hydrogen chloride (6 ml) and methanol (6 ml) were added
  4. stirringthe reaction mixture was stirred at 100° C. for 2 hours
  5. temperatureThe reaction mixture was cooled
  6. concentrationThe mixture was concentrated under reduced pressure
  7. extractionthe product was extracted with ethyl acetate
  8. washThe organic layer was washed with saturated brine
  9. customdried
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was isolated
  12. custompurified by silica gel column chromatography (acetone:methanol=20:1)

출처 및 근거

ORD 기록
ord-19caceb67bd04323be69a9591db73262
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07622487B2

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