3,4-Dimethoxyphenyl methyl ketone → 4-[1-(3,4-Dimethoxyphenyl)ethyl]piperazine

HRID 967028Notes

Reaction equation

HRID 967028 reaction equation
ClC1C=CC([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=CC=1C(F)(F)F.[CH3:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH3:30])[CH:22]=1)=O.[BH4-].[Na+]>CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C.CO>[CH3:30][O:29][C:23]1[CH:22]=[C:21]([CH:19]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH3:18])[CH:26]=[CH:25][C:24]=1[O:27][CH3:28]

Participants

6

Reactant 3

HCID 143283,4-Dimethoxyphenyl methyl ketoneHCID 27781371-(4-Chloro-3-(trifluoromethyl)phenyl)piperazineHCID 4311764Sodium borohydride

Product 1

HCID 27584404-[1-(3,4-Dimethoxyphenyl)ethyl]piperazine

Reagents, catalysts & solvents 2

HCID 178460666HCID 178460666, compoundCatalystHCID 887MethanolSolvent

Procedure

A quantity of 0.17 g (0.6 mmole, 1 eq) of 1-(4-chloro-3-trifluoromethyl-phenyl)-piperazine and 0.1 g (0.6 mmole, 1 eq) of 3,4-dimethoxyacetophenone and 2 mL of Ti(OiPr)4 are warmed to 70° C. for 2 hours. The reaction solution is cooled to room temperature and 20 mL of anhydrous methanol is added followed by 1.0 g of NaBH4 and the resulting solution is stirred at room temperature for 2 hours. The reaction is quenched by the addition of 1 N NaOH and extracted with CH2Cl2. The CH2Cl2 extracts are dried over anhydrous MgSO4 and concentrated in vacuo. The residue is chromatographed on SiO2 with ethyl to afford 1-[4-chloro-3-trifluoromethyl)phenyl]-4-[1-(3,4-dimethoxyphenyl)ethyl]piperazine (compound 2). Analysis 1H NMR (400 MHz, CDCl3): 7.31 (1H, d), 7.19 (1H, m), 6.90 (4H, m), 3.89 (6H, d), 3.38 (1H, m), 3.20 (4H, m), 2.61 (4H, m). MS (LC-MS): Calculated for C21H24ClF3N2O2 428.88, found 429.30 (M+). III. 3-{1-4-(4-Bromo-3-methoxy-phenyl)-piperazin-1-yl]-ethyl}-quinoline via Scheme C

Workup

  1. customThe reaction is quenched by the addition of 1 N NaOH
  2. extractionextracted with CH2Cl2
  3. dry with materialThe CH2Cl2 extracts are dried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is chromatographed on SiO2 with ethyl

Sources & evidence

ORD record
ord-4c06c5586e27406b9e2fab6efcb8b104
Source dataset
uspto-grants-2005_10
Patent number
US06953801B2

Reaction notes

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