Ethyl isocyanate → N-ethyl-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)-1-piperidinecarboxamide

HRID 748807Notes

Reaction equation

HRID 748807 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([C:12]2([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH2:33]([N:35]=[C:36]=[O:37])[CH3:34].C(=O)(O)[O-].[Na+]>ClCCl.C(OC(C)C)(C)C>[CH2:33]([NH:35][C:36]([N:15]1[CH2:16][CH2:17][C:12]([S:9]([C:6]2[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][CH:5]=2)(=[O:10])=[O:11])([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=2[F:25])[CH2:13][CH2:14]1)=[O:37])[CH3:34]

Participants

7

Reactant 4

HCID 8022Ethyl isocyanateHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 692029464-[(4-Chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)piperidine Hydrochloride

Product 1

HCID 59750838N-ethyl-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)-1-piperidinecarboxamideYield 85%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7914Diisopropyl EtherSolvent

Procedure

The 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)piperidine hydrochloride (80 mg, 0.20 mmol) obtained in Example 260 and triethylamine (0.092 ml, 0.66 mmol) were dissolved in dichloromethane (4 ml), followed by the addition of ethyl isocyanate (0.027 ml, 0.34 mmol) at room temperature. After stirring at room temperature for 6 hours, a saturated aqueous solution of sodium bicarbonate (0.5 ml) was added. The residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash silica gel chromatography, and the fraction obtained from the dichloromethane:methanol=50:1 eluate was concentrated under reduced pressure to give a white solid. The resulting solid was washed with diisopropyl ether, whereby the title compound (74 mg, 0.17 mmol, 85%) was obtained as a white powder.

Workup

  1. customThe residue obtained
  2. concentrationby concentrating the reaction mixture under reduced pressure
  3. customthe fraction obtained from the dichloromethane
  4. concentrationmethanol=50:1 eluate was concentrated under reduced pressure
  5. customto give a white solid

Sources & evidence

ORD record
ord-59ebad614a6a47d58501e596b634a73a
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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