Diisopropylamine → 1-(6-Chloro-2-hexanone-1-sulfonyl)-4-(4-fluorophenyl)piperazine
Reaction equation
[Li+].CC([N-]C(C)C)C.C([Li])CCC.C(NC(C)C)(C)C.[F:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][N:31]([S:34]([CH3:37])(=[O:36])=[O:35])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.[Cl:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43](Cl)=[O:44]>C1COCC1.CCOC(C)=O>[Cl:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43](=[O:44])[CH2:37][S:34]([N:31]1[CH2:32][CH2:33][N:28]([C:25]2[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=2)[CH2:29][CH2:30]1)(=[O:35])=[O:36]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -78 °C
Procedure
To a solution of LDA (51 mmol, prepared by slow addition of n-butyl lithium (20.4 ml, 2.5M in hexane, 51 mmol) to a solution of diisopropylamine (5.16 g, 51 mmol) in THF (30 ml) at −78° C.) at −78° C. was added a solution of 1-(4-fluorophenyl)4-(methanesulfonyl)-piperazine (6 g, 23.2 mmol) in THF (150 ml). The mixture was stirred for 1 h at −78° C. A solution of 5-chlorovaleryl chloride (4 g, 25.8 mmol) in THF (20 ml) was added dropwise. The mixture was stirred at −78° C. for 1 h and at room temperature for 18 h. The solution was diluted with EtOAc and washed with sat. NH4Cl and brine and dried over MgSO4. Chromatography of the residue on silica gel (eluant: EtOAc—CH2Cl2— petroleum ether (15:35:50)) afforded 1-(6-chloro-2-hexanone-1-sulfonyl)-4-(4-fluorophenyl)piperazine (5.22 g, 60%) as white crystals: MS (ESI): 399 (MNa+).
Workup
- stirringThe mixture was stirred at −78° C. for 1 h and at room temperature for 18 h
- washwashed with sat. NH4Cl and brine
- dry with materialdried over MgSO4
Sources & evidence
- ORD record
- ord-09a5bc7c7a6b48a7be2af349fbdf7e13
- Source dataset
- uspto-grants-2004_05
- Patent number
- US06734184B1
Reaction notes
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