4-(Trifluoromethoxy)aniline → (5SR,6RS)-8-benzyl-6-hydroxy-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 1260482Notes

Reaction equation

HRID 1260482 reaction equation
C(O[C:4]([C:6]1([CH2:20][CH2:21]OC)[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH:7]1[OH:19])=[O:5])C.[F:24][C:25]([F:35])([F:34])[O:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1.[Cl-].C[Al+]C>C1(C)C=CC=CC=1>[CH2:12]([N:9]1[CH2:10][CH2:11][C:6]2([C:4](=[O:5])[N:31]([C:30]3[CH:32]=[CH:33][C:27]([O:26][C:25]([F:24])([F:34])[F:35])=[CH:28][CH:29]=3)[CH2:21][CH2:20]2)[CH:7]([OH:19])[CH2:8]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 6008484-(Trifluoromethoxy)anilineHCID 16686359Dimethylalumanylium chlorideHCID 580566191-Benzyl-3-hydroxy-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 56602659(5SR,6RS)-8-benzyl-6-hydroxy-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-oneYield 77%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of (3RS,4SR)-1-benzyl-3-hydroxy-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (618 mg, 1.92 mmol) and 4-(trifluoromethoxy)aniline (516 μL, 3.85 mmol) in toluene (5 ml) under an argon atmosphere at room temperature, was added dimethylaluminium chloride (0.9M solution in heptane, 4.27 ml, 3.85 mmol) and the mixture was refluxed for 4 hours. The reaction mixture was cooled to room temperature and quenched with sat. Na2SO4 (aq) solution and the mixture was filtered through Celite® and evaporated under reduced pressure. The crude residue was purified by flash column chromatography (1:1 AcOEt/heptane) to give (5SR,6RS)-8-benzyl-6-hydroxy-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (620 mg, 77%) as a white solid. MS (ESI): 405.4 (MH+).

Workup

  1. temperaturethe mixture was refluxed for 4 hours
  2. customquenched with sat. Na2SO4 (aq) solution
  3. filtrationthe mixture was filtered through Celite®
  4. customevaporated under reduced pressure
  5. customThe crude residue was purified by flash column chromatography (1:1 AcOEt/heptane)

Sources & evidence

ORD record
ord-18b109bb256649c3860189b09fcfd03e
Source dataset
uspto-grants-2013_06
Patent number
US08470843B2

Reaction notes

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