4-Chloroaniline → tert-Butyl 4-{[(4-chlorophenyl)amino]carbonyl}piperidine-1-carboxylate

HRID 419844Notes

Reaction equation

HRID 419844 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].[Cl:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C(#N)C>[Cl:17][C:18]1[CH:24]=[CH:23][C:21]([NH:22][C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:13][CH2:12]2)=[O:16])=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 78124-ChloroanilineHCID 8471TriethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 29201912tert-Butyl 4-{[(4-chlorophenyl)amino]carbonyl}piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-BOC-piperidine-4-carboxylic acid (100 g, 437 mmol), 4-chloroaniline (61.2 g, 480 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (100 g, 524 mmol) and triethylamine (182.6 mL, 1.31 mol) were dissolved in cold (10° C.) acetonitrile (1.75 L). The reaction mixture was stirred for 54 hours at room temperature and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and then partitioned with 2N hydrochloric acid. The resulting precipitate was filtered off, re-dissolved in dichloromethane, the solution was dried over MgSO4 and evaporated under reduced pressure. The residue was triturated with ether to afford the desired compound as a white solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. custompartitioned with 2N hydrochloric acid
  4. filtrationThe resulting precipitate was filtered off
  5. dissolutionre-dissolved in dichloromethane
  6. dry with materialthe solution was dried over MgSO4
  7. customevaporated under reduced pressure
  8. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-69f550a6f47248bc883e90b6f87f66d4
Source dataset
uspto-grants-2012_01
Patent number
US08093400B2

Reaction notes

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