Lithium Hydroxide → HCID 15547323, compound

HRID 429214Notes

Reaction equation

HRID 429214 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Cl)=[CH:4][CH:3]=1.[C:10](=[O:13])([O-])[O-:11].[Na+].[Na+].[OH-].[Li+].[C:18](#[N:20])[CH3:19]>CO.O>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:20]2[CH2:4][CH2:3][CH:2]([CH2:9][C:10]([OH:11])=[O:13])[CH2:19][CH2:18]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 6342AcetonitrileHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 10340Sodium Carbonate

Product 1

HCID 15547323HCID 15547323, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Ethyl-4-pyridylacetate (5 g) is dissolved in ethanol (30 mL), treated with platinum oxide catalyst (30 mg) and hydrogenated on a Parr apparatus for 4 hr. The catalyst is filtered off and the ethyl-4-piperidinylacetate is isolated by removal of the solvent under vacuum. This material is then dissolved in acetonitrile (50 mL) and treated with 4-chlorobenzyl chloride (4.9 g) and sodium carbonate (10 g). The resulting mixture is heated in methanol (30 mL) and treated with a solution of lithium hydroxide (2 g) in water (10 mL). The mixture is allowed to stand overnight. Addition of 47.6 mL of 1 N HCI solution followed by concentration and extraction of the residue with chloroform provides the desired 1-(4-chlorobenzyl)-4-piperidylacetic acid. A portion of this material (1 g) is dissolved in methylene chloride and treated with 1,1′-carbonyldiimidazole (0.65 g) and allowed to stand overnight. This solution is then treated with 2-methylindoline (0.5 g). After 2 h the resulting mixture is washed 3 times with water dried and concentrated. Purification by column chromatography on silica gel provides 1.2 g of the desired 2-(1-[4-chlorobenzyl]piperidin-4-yl)-1-(2-methylindolin-1-yl)-1-ethanone (Compound 1). The dihydrochloride salt is subsequently prepared (Compound 1a).

Workup

  1. additionAddition of 47.6 mL of 1 N HCI solution
  2. concentrationfollowed by concentration and extraction of the residue with chloroform

Sources & evidence

ORD record
ord-a939d0b2b6c74f48a413ab1dfe5c8cad
Source dataset
uspto-grants-2001_11
Patent number
US06316470B1

Reaction notes

Loading…