o-Chlorophenylacetic acid → 4-(2-Bromo-5-hydroxybenzyl)-1-[(2-chlorophenyl)acetyl]piperidine

HRID 1006062Notes

Reaction equation

HRID 1006062 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[Br:34][C:35]1[CH:47]=[CH:46][C:45]([OH:48])=[CH:44][C:36]=1[CH2:37][CH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>CN(C)C=O>[Br:34][C:35]1[CH:47]=[CH:46][C:45]([OH:48])=[CH:44][C:36]=1[CH2:37][CH:38]1[CH2:39][CH2:40][N:41]([C:9](=[O:11])[CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[Cl:1])[CH2:42][CH2:43]1

Participants

6

Reactant 4

HCID 17124o-Chlorophenylacetic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 99433374-Bromo-3-[(piperidin-4-yl)methyl]phenol2×

Product 1

HCID 226753214-(2-Bromo-5-hydroxybenzyl)-1-[(2-chlorophenyl)acetyl]piperidineYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In N,N-dimethylformamide (10 ml) were dissolved 4-(2-bromo-5-hydroxybenzyl)piperidine (the compound of Example 10) (2010.9 mg, 7.500 mmol), 2-chlorophenylacetic acid (1279.5 mg, 7.500 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (1716.3 mg, 9.000 mmol) and 1-hydroxybenzotriazole (1114.8 mg, 7.500 mmol), and the resulting solution was stirred at room temperature for 5 hours. The reaction was terminated by adding water (100 ml), followed by extraction with a toluene-diethyl ether mixture (1:1). The organic layer was washed successively with a 5% aqueous sodium hydrogensulfate solution, a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent, whereby the title compound (2754.4 mg, 6.547 mmol) was obtained in a yield of 87%.

Workup

  1. customThe reaction was terminated
  2. additionby adding water (100 ml)
  3. extractionfollowed by extraction with a toluene-diethyl ether mixture (1:1)
  4. washThe organic layer was washed successively with a 5% aqueous sodium hydrogensulfate solution
  5. dry with materiala saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate
  6. distillationdistilled under reduced pressure

Sources & evidence

ORD record
ord-95554bc7268e43d682f814ad19ec2fac
Source dataset
uspto-grants-2004_09
Patent number
US06787560B2

Reaction notes

Loading…