Aniline → 1,1-Dimethylethyl 3-[(phenylamino)carbonyl]-1-piperidinecarboxylate

HRID 32306

Reaction equation

HRID 32306 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([Li])CCC.[Cl-].[NH4+]>ClCCl.O1CCCC1.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:16])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 6

HCID 6115AnilineHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 27356471-((Tert-butoxy)carbonyl)piperidine-3-carboxylic acidHCID 178418339Butyllithium

Product 1

HCID 181042161,1-Dimethylethyl 3-[(phenylamino)carbonyl]-1-piperidinecarboxylateYield 71.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-t-butoxycarbonyl-3-piperidinecarboxylic acid (458 mg, 2.00 mmol), sodium hydride (88 mg, 2.20 mmol, 60% oil suspension), oxalyl chloride (0.22 ml, 2.50 mmol) and catalytic amount of dimethylformamide (0.20 ml) in dichloromethane (16 ml) was stirred at 0° C. After stirring for 30 min, aniline (0.20 ml, 2.20 mmol) which was treated with n-butyl lithium (1.45 ml, 2.30 mmol, 1.59 M in hexane) in tetrahydrofuran (4 ml) was added to the reaction mixture at 0° C. After additional 30 min, saturated ammonium chloride was added and the whole reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and evaporated in vacuo. Purification of the residue by silica gel column chromatography (hexane-ethyl acetate) gave 1-t-butoxycarbonylpiperidine-3-carboxanilide (437 mg, 71%).

Workup

  1. additionwas added to the reaction mixture at 0° C
  2. waitAfter additional 30 min
  3. customthe whole reaction mixture
  4. extractionwas extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo
  8. customPurification of the residue by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-a88a0fed15574da5a6c98d871c7d89ff
Source dataset
uspto-grants-2008_09
Patent number
US07427615B2

Linked notes

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