Potassium Carbonate → HCID 66758680, compound

HRID 523035Notes

Reaction equation

HRID 523035 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:16])[CH2:13][CH2:12][NH:11][CH2:10][C:9]2([CH3:15])[CH3:14])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:24][CH2:25][CH:26]=[C:27]1[C:33]2[CH:34]=[CH:35][CH:36]=[N:37][C:32]=2[CH2:31][O:30][C:29]2[CH:38]=[CH:39][C:40]([C:42](=[O:44])[CH3:43])=[CH:41][C:28]1=2>C(#N)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:16])[CH2:13][CH2:12][N:11]([CH2:24][CH2:25][CH:26]=[C:27]3[C:33]4[CH:34]=[CH:35][CH:36]=[N:37][C:32]=4[CH2:31][O:30][C:29]4[CH:38]=[CH:39][C:40]([C:42](=[O:44])[CH3:43])=[CH:41][C:28]3=4)[CH2:10][C:9]2([CH3:14])[CH3:15])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 18437142(S)-4-(4-chlorophenyl)-3,3-dimethylpiperidin-4-olHCID 66758314HCID 66758314, compound

Product 1

HCID 66758680HCID 66758680, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a suspension of the (S)-4-(4-chloro-phenyl)-3,3-dimethyl-piperidin-4-ol (5.50 g, 22.94 mmol) in acetonitrile (200 mL) and water (50 mL) was added potassium carbonate (7.17 g, 51.9 mmol) followed by solid 1-[5-(3-bromo-propylidene)-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl]-ethanone (6.30 g, 17.3 mmol). The heterogeneous mixture was stirred at room temperature 4 hours, warmed to 50° C. and stirred 13 hours. The mixture was cooled to room temperature and acetonitrile was removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (750 mL) and the extract was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (3:1 ethyl acetate:hexanes) to afford (S)-1-(5-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl)-ethanone as an off-white solid.

Workup

  1. temperaturewarmed to 50° C.
  2. stirringstirred 13 hours
  3. temperatureThe mixture was cooled to room temperature
  4. customacetonitrile was removed under reduced pressure
  5. extractionThe aqueous layer was extracted with ethyl acetate (750 mL)
  6. washthe extract was washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified by silica gel chromatography (3:1 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-77f0858f147041c4bda9c3eae4716af4
Source dataset
uspto-grants-2016_05
Patent number
US09334283B2

Reaction notes

Loading…