2-(4-Chlorophenoxy)aniline → 1-Acetyl-N-(3-(1-(2-(4-chlorophenoxy)phenylamino)ethyl)phenyl)piperidine-4-carboxamide

HRID 1043031

Reaction equation

HRID 1043031 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[NH2:9])=[CH:4][CH:3]=1.[C:16]([N:19]1[CH2:24][CH2:23][CH:22]([C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([C:34](=O)[CH3:35])[CH:29]=2)=[O:26])[CH2:21][CH2:20]1)(=[O:18])[CH3:17].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCl.C(O)(=O)C.[Cl-].C(O[Ti+](OC(C)C)OC(C)C)(C)C>[C:16]([N:19]1[CH2:24][CH2:23][CH:22]([C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH:34]([NH:9][C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[O:6][C:5]3[CH:14]=[CH:15][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH3:35])[CH:29]=2)=[O:26])[CH2:21][CH2:20]1)(=[O:18])[CH3:17]

Participants

8

Reactant 4

HCID 760102-(4-Chlorophenoxy)anilineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 402184231-acetyl-N-(3-acetylphenyl)piperidine-4-carboxamide

Product 1

HCID 595716781-Acetyl-N-(3-(1-(2-(4-chlorophenoxy)phenylamino)ethyl)phenyl)piperidine-4-carboxamideYield 18%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 3084342Chlorotitanium triisopropoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

2-(4-Chlorophenoxy)aniline (137 mg, 0.6237 mmol, 1.1 eq) and 1-acetyl-N-(3-acetylphenyl)piperidine-4-carboxamide (160 mg, 0.5549 mmol, 1 eq) were stirred in dry dichloromethane (DCM) at room temperature for 10 min. Tri-isopropoxytitanium chloride (295 μL, 1.2351 mmol, 2.2 eq) was added to the reaction mixture which was stirred at room temperature for an additional 10 min. Sodium triacetoxyborohydride (590 mg, 2.7838 mmol, 5 eq) and acetic acid (3 drops) were added to the reaction mixture which was stirred at room temperature for 16 h. The reaction mixture was then poured onto a solution of saturated aqueous sodium bicarbonate (100 mL) and extracted with DCM (80 mL). The organic layer was washed with brine (100 mL), dried over MgSO4, filtered and concentrated to give the crude as a yellow oil. Purification of the crude by flash chromatography (ISCO) eluting with a gradient [from 100% petroleum ether (PE) to 100% EtOAc] gave the title compound (48 mg, 18%) as a clear oil.

Workup

  1. stirringwas stirred at room temperature for 16 h
  2. extractionextracted with DCM (80 mL)
  3. washThe organic layer was washed with brine (100 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude as a yellow oil
  8. customPurification of the crude by flash chromatography (ISCO)
  9. washeluting with a gradient [from 100% petroleum ether (PE) to 100% EtOAc]

Sources & evidence

ORD record
ord-3070a69fa6bc4992aa570315dc4b501b
Source dataset
uspto-grants-2013_10
Patent number
US08558028B2

Linked notes

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