Potassium Carbonate → HCID 22012231, compound

HRID 1377497Notes

Reaction equation

HRID 1377497 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C(C)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:9][CH2:10][N:11]([CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:12][CH2:13]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 68320Ethyl 3-bromopropionateHCID 27591364-(4-Fluorophenyl)piperidine

Product 1

HCID 22012231HCID 22012231, compoundYield 111.2%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 4-(4-fluorophenyl)-piperidine (15 g), ethyl 3-bromopropionate (20 g), and potassium carbonate (14 g) in methyl isobutyl ketone was refluxed for 16 h. Filtration and removal of solvent in vacuo gave 26 g of crude ethyl 3-(4-(4-fluorophenyl)-1-piperidyl)propionate as an oil which was used directly in the next step. The oil was dissolved in dry tetrahydrofuran (70 ml) and added dropwise to a suspension of lithium aluminium hydride (6.5 g) in dry tetrahydrofuran (250 ml) at 15° C. under nitrogen gas. After stirring for 30 min at room temperature, water (6.5 ml), 10N sodium hydroxide (7 ml), and water (30 ml) were added, subsequently. Filtration and removal of solvent gave 20 g of crude 3-(4-(4-fluorophenyl)-1-piperidyl)-1-propanol as an oil which was sufficiently pure for use in the next step. A solution of 3-(4-(4-fluorophenyl)-1-piperidyl)-1-propanol (10 g) in dry toluene (150 ml) was treated portionwise with a 50% xylene suspension of sodium hydride (3 g). A solution of 3-chloro-1,2-benzisothiazole (3.6 g) in dry toluene (30 ml) was added dropwise at room temperature followed by stirring for 1.5 h at room temperature. Ice was added, the phases separated and the aqueous phase extracted with ether.

Workup

  1. temperaturewas refluxed for 16 h
  2. filtrationFiltration and removal of solvent in vacuo

Sources & evidence

ORD record
ord-734911a4e84b4e97bdb38033c0c60c6d
Source dataset
uspto-grants-1997_09
Patent number
US05665725

Reaction notes

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