4-Fluoroaniline → 2-(4-Dimethylamino-4-phenyl-cyclohexyl)-N-(4-fluoro-phenyl)-acetamide

HRID 908996Notes

Reaction equation

HRID 908996 reaction equation
C([Li])CCC.[F:6][C:7]1[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=1.C([O:16][C:17](=O)[CH2:18][CH:19]1[CH2:24][CH2:23][C:22]([N:31]([CH3:33])[CH3:32])([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:21][CH2:20]1)C.[Cl-].[NH4+]>C1COCC1>[CH3:33][N:31]([CH3:32])[C:22]1([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:23][CH2:24][CH:19]([CH2:18][C:17]([NH:11][C:10]2[CH:12]=[CH:13][C:7]([F:6])=[CH:8][CH:9]=2)=[O:16])[CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 97314-FluoroanilineHCID 25517Ammonium ChlorideHCID 67386781(4-Dimethylamino-4-phenyl-cyclohexyl)-acetic acid ethyl esterHCID 178418339Butyllithium

Product 1

HCID 117180822-(4-Dimethylamino-4-phenyl-cyclohexyl)-N-(4-fluoro-phenyl)-acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (1.6 M solution in hexane; 11.9 ml; 19 mmol) was added dropwise at 0° C. to a solution of 4-fluoroaniline (1.06 g; 9.5 mmol) in 10 ml THF. The mixture was allowed to come to RT and was subsequently stirred for 1 h. A solution of (4-dimethylamino-4-phenyl-cyclohexyl)-acetic acid ethyl ester (2.5 g; 8.6 mmol) in 15 ml THF was added dropwise at −78° C. The mixture was subsequently stirred for 1 h and then allowed to come to RT. It was hydrolysed with ammonium chloride solution and extracted with MC. After concentration, the crude product was taken up in ether. A solid then remained (less polar diastereoisomer; 1.37 g; 45%); the supernatant was chromatographed on silica gel (eluent:ether). 315 mg (10%) of the more polar diastereoisomer were obtained.

Workup

  1. customto come to RT
  2. stirringThe mixture was subsequently stirred for 1 h
  3. customto come to RT
  4. extractionextracted with MC
  5. concentrationAfter concentration
  6. customthe supernatant was chromatographed on silica gel (eluent:ether)
  7. custom315 mg (10%) of the more polar diastereoisomer were obtained

Sources & evidence

ORD record
ord-0650c8be03024ad6aba0f312fc4152f7
Source dataset
uspto-grants-2011_09
Patent number
US08017630B2

Reaction notes

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