Diethyl chlorophosphate → 4-(4-Fluorophenyl)-1-[2-(1-t-butoxycarbonylpiperidin-4-yl)-ethenylsulphonyl]-piperazine

HRID 895381Notes

Reaction equation

HRID 895381 reaction equation
C([Li])CCC.[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][N:16]([S:19]([CH3:22])(=[O:21])=[O:20])[CH2:15][CH2:14]2)=[CH:9][CH:8]=1.C(OP(Cl)(OCC)=O)C.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42]([CH:45]=O)[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[F:6][C:7]1[CH:8]=[CH:9][C:10]([N:13]2[CH2:18][CH2:17][N:16]([S:19]([CH:22]=[CH:45][CH:42]3[CH2:43][CH2:44][N:39]([C:37]([O:36][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:38])[CH2:40][CH2:41]3)(=[O:20])=[O:21])[CH2:15][CH2:14]2)=[CH:11][CH:12]=1

Participants

8

Reactant 5

HCID 13139Diethyl chlorophosphateHCID 25517Ammonium ChlorideHCID 6690391-(4-Fluorophenyl)-4-(methylsulfonyl)piperazineHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 178418339Butyllithium2×

Product 1

HCID 541807894-(4-Fluorophenyl)-1-[2-(1-t-butoxycarbonylpiperidin-4-yl)-ethenylsulphonyl]-piperazine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

n-Butyl lithium (8.6 ml of a 1.6 M solution in THF) was added dropwise to a suspension of 4-(4-fluorophenyl)-1-methanesulphonylpiperazine (3.52 g) in THF (40 ml) at −78° C. and the mixture was stirred for 30 minutes. Diethylchlorophosphate (1.97 ml) was added dropwise and the mixture was stirred at −78° C. for a further 30 minutes. n-Butyl lithium (8.6 ml of a 1.6 M solution in THF) was added dropwise and stirred for 30 minutes. A solution of 1-(t-butoxycarbonyl)-piperidine-4-aldehyde (2.91 g) in THF (5 ml) was added dropwise and the mixture was allowed to warm to ambient temperature and was stired for 10 hours. Saturated aqueous ammonium chloride solution (5 ml) was added, the reaction mixture was diluted with ethyl acetate (25 ml) and washed with water. Removal of the solvent gave 4-(4-fluorophenyl)-1-[2-(1-t-butoxycarbonylpiperidin-4-yl)-ethenylsulphonyl]-piperazine as a gum which solidified on standing, M+H=455 (454).

Workup

  1. stirringthe mixture was stirred at −78° C. for a further 30 minutes
  2. stirringstirred for 30 minutes
  3. waitwas stired for 10 hours
  4. washwashed with water
  5. customRemoval of the solvent

Sources & evidence

ORD record
ord-54ba7607942d48a7b0b3317f84b2e66f
Source dataset
uspto-grants-2005_07
Patent number
US06916817B1

Reaction notes

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