Cyanomethylenetributylphosphorane → t-Butyl 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)-1-piperidinecarboxylate

HRID 748801Notes

Reaction equation

HRID 748801 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=2[F:32])[CH2:12][CH2:13][N:14]([CH2:22][CH2:23]O)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1.C(OCC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2([C:25]3[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=3[F:32])[CH2:23][CH2:22][N:14]([C:15]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:21])[CH2:13][CH2:12]2)(=[O:9])=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 4622928Cyanomethylenetributylphosphorane2×HCID 59750811t-Butyl N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)propyl]-N-(2-hydroxyethyl)carbamate

Product 1

HCID 59750843t-Butyl 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)-1-piperidinecarboxylateYield 74%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

The t-butyl N-[3-[(4-chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)propyl]-N-(2-hydroxyethyl)carbamate (200 mg, 0.404 mmol) obtained in Example 257 was dissolved in toluene (10 ml), followed by the addition of cyanomethylenetri-n-butylphosphorane (200 mg, 0.829 mmol). Under an argon atmosphere, the resulting mixture was heated under reflux for 8 hours. After the reaction mixture was allowed to cool down, cyanomethylenetri-n-butylphosphorane (200 mg, 0.829 mmol) was added thereto. Under an argon atmosphere, the mixture was heated under reflux for 14 hours. After the reaction mixture was allowed to cool down, the residue obtained by concentrating the reaction mixture under reduced pressure was subjected to flash silica gel chromatography, and the fraction obtained from the hexane:ethyl acetate=4:1 eluate was concentrated under reduced pressure to give a white solid. The white solid was washed with diethyl ether, whereby the title compound (140 mg, 0.297 mmol, 74%) was obtained as a white powder.

Workup

  1. temperatureUnder an argon atmosphere, the resulting mixture was heated
  2. temperatureunder reflux for 8 hours
  3. temperatureto cool down
  4. temperatureUnder an argon atmosphere, the mixture was heated
  5. temperatureunder reflux for 14 hours
  6. temperatureto cool down
  7. customthe residue obtained
  8. concentrationby concentrating the reaction mixture under reduced pressure
  9. customthe fraction obtained from the hexane
  10. concentrationethyl acetate=4:1 eluate was concentrated under reduced pressure
  11. customto give a white solid

Sources & evidence

ORD record
ord-e1ad089e08e446e1bfbd514ac1b4d843
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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