Dicyclohexylcarbodiimide → 4-[3-(4-Fluoro-phenoxy)-phenylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 29882

Reaction equation

HRID 29882 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1(N=C=NC2CCCCC2)CCCCC1.ON1C2N=CC=CC=2N=N1.[F:42][C:43]1[CH:56]=[CH:55][C:46]([O:47][C:48]2[CH:49]=[C:50]([NH2:54])[CH:51]=[CH:52][CH:53]=2)=[CH:45][CH:44]=1>C(OCC)(=O)C.CN(C)C=O>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:16])[NH:54][C:50]2[CH:51]=[CH:52][CH:53]=[C:48]([O:47][C:46]3[CH:55]=[CH:56][C:43]([F:42])=[CH:44][CH:45]=3)[CH:49]=2)[CH2:12][CH2:13]1)=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 181649HOAtHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 235060153-(4-Fluorophenoxy)aniline

Product 1

HCID 692223994-[3-(4-Fluoro-phenoxy)-phenylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl esterYield 86%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a mixture of N-Boc piperidine-4-carboxylic acid (9.2 g, 0.04 mol) and DCC (dicyclohexylcarbodiimide) (8.2 g, 0.04 mol) in ethyl acetate (150 mL) was added HOAt (1-hydroxy-7-azabenzotriazole) (5.5 g, 0.04 mol) in DMF (dimethylformamide) (40 mL). The mixture was stirred at room temperature for 10 minutes and then 3-(4-fluoro-phenoxy)-phenylamine (8.7 g, 0.043 mol) in ethyl acetate (50 mL) was added. The reaction mixture was allowed to stir overnight at room temperature and then was concentrated to remove most of the ethyl acetate. The precipitated solid was removed by filtration through Celite. The filtrate was diluted with ethyl acetate and washed with 1 N HCl, saturated NaHCO3 and brine (3×60 mL). The organic phase was dried with MgSO4 and concentrated. The residue was purified on silica eluting with 20% ethyl acetate/hexanes to afford 4-[3-(4-fluoro-phenoxy)-phenylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester (14.2 g, 86%) as an off-white solid.

Workup

  1. stirringto stir overnight at room temperature
  2. concentrationwas concentrated
  3. customto remove most of the ethyl acetate
  4. customThe precipitated solid was removed by filtration through Celite
  5. additionThe filtrate was diluted with ethyl acetate
  6. washwashed with 1 N HCl, saturated NaHCO3 and brine (3×60 mL)
  7. dry with materialThe organic phase was dried with MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified on silica eluting with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-84507a2f79af4d63910083e8ec979cf9
Source dataset
uspto-grants-2008_09
Patent number
US07423043B2

Linked notes

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