Hydrochloric Acid → HCID 131731754, compound

HRID 2403549Notes

Reaction equation

HRID 2403549 reaction equation
[K].[C:2](#[N:4])[CH3:3].C([O:7][C:8](=O)[CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)[CH2:20][CH2:19]2)[CH2:12][CH2:11]1)C.[ClH:35]>O1CCCC1.C(OCC)(=O)C>[ClH:35].[ClH:35].[O:7]=[C:8]([CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][CH2:17][N:18]2[CH2:19][CH2:20][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)[CH2:22][CH2:23]2)[CH2:12][CH2:11]1)[CH2:3][C:2]#[N:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 5462222PotassiumHCID 24781220HCID 24781220, compound

Product 1

HCID 131731754HCID 131731754, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 0.77 mL (1.3 mmol) of potassium tert-pentoxyde solution (1.7M in toluene) is added dropwise at room temperature to a stirred solution of 52 mg (1.27 mmol) of acetonitrile in 2.5 mL of tetrahydrofuran followed by dropwise addition of 0.19 g (0.44 mmol) of (4-{2-[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethyl}piperidin-1-yl)acetic acid ethyl ester in 1 mL of tetrahydrofuran. After 30 minutes at room temperature, the reaction mixture is diluted with 10 mL of an aqueous 0.2N aqueous hydrochloric acid solution and 50 mL of ethyl acetate forming an emulsion. The mixture is concentrated under reduced pressure and the product is purified over 10 g of silica gel (eluant dichloromethane/methanol 95/5). The oily product is dissolved in 2 mL of diethyl ether and acidified with a hydrochloric acid diethyl ether solution. The precipitate is filtered, washed with diethyl ether and dried under reduced pressure to give 30 mg (14%) of 3-oxo-4-(4-{2[4-(3-trifluoromethylphenyl)piperazin-1-yl]ethyl}piperidin-1-yl)butanenitrile, dihydrochloride.

Workup

  1. concentrationThe mixture is concentrated under reduced pressure
  2. customthe product is purified over 10 g of silica gel (eluant dichloromethane/methanol 95/5)
  3. dissolutionThe oily product is dissolved in 2 mL of diethyl ether
  4. filtrationThe precipitate is filtered
  5. washwashed with diethyl ether
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-7b89de86502e4c67af8121e2c2e96b60
Source dataset
uspto-grants-2014_08
Patent number
US08802678B2

Reaction notes

Loading…