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

HRID 1043030

Reaction equation

HRID 1043030 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]=[CH:30][C:29]=2[C:34](=O)[CH3:35])=[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]=[CH:30][C:29]=2[CH:34]([NH:9][C:8]2[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=2[O:6][C:5]2[CH:14]=[CH:15][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH3:35])=[O:26])[CH2:21][CH2:20]1)(=[O:18])[CH3:17]

Participants

8

Reactant 4

HCID 760102-(4-Chlorophenoxy)anilineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 171457861-acetyl-N-(2-acetylphenyl)piperidine-4-carboxamide

Product 1

HCID 426136031-Acetyl-N-(2-(1-(2-(4-chlorophenoxy)phenylamino)ethyl)phenyl)piperidine-4-carboxamideYield 10%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 3084342Chlorotitanium triisopropoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

2-(4-Chlorophenoxy)aniline (25 mg, 0.1138 mmol, 1.1 eq) and 1-acetyl-N-(2-acetylphenyl)piperidine-4-carboxamide (30 mg, 0.1040 mmol, 1 eq) were stirred in dry dichloromethane (DCM) at room temperature for 10 min. Tri-isopropoxytitanium chloride (55 μL, 0.2303 mmol, 2.2 eq) was added to the reaction mixture which was stirred at room temperature for an additional 10 min. Sodium triacetoxyborohydride (110 mg, 0.5190 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 (50 mL) and extracted with DCM (30 mL). The organic layer was washed with brine (50 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 (5 mg, 10%) as a clear oil.

Workup

  1. stirringwas stirred at room temperature for 16 h
  2. extractionextracted with DCM (30 mL)
  3. washThe organic layer was washed with brine (50 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-9efb7f91417d4f318acce73adabc7f10
Source dataset
uspto-grants-2013_10
Patent number
US08558028B2

Linked notes

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