Lithium Hexamethyldisilazide → HCID 178461578, compound

HRID 1047362Notes

Reaction equation

HRID 1047362 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([OH:17])[CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:18]([F:21])([F:20])[F:19])([O-:3])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl[CH2:33][C:34]([N:36]1[CH2:41][C@@H:40]([CH3:42])[N:39]([C:43]2[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][CH:44]=2)[CH2:38][C@@H:37]1[CH3:53])=[O:35]>CN(C)C=O.O1CCCC1.C(OCC)C>[CH3:53][C@H:37]1[CH2:38][N:39]([C:43]2[CH:44]=[CH:45][C:46]([C:49]([F:52])([F:50])[F:51])=[CH:47][CH:48]=2)[C@H:40]([CH3:42])[CH2:41][N:36]1[C:34](=[O:35])[CH2:33][O:17][C@H:14]1[CH2:15][CH2:16][C@H:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:18]([F:19])([F:20])[F:21])[CH:6]=2)[CH2:12][CH2:13]1

Participants

7

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 668521722-Chloro-1-[trans-2,5-dimethyl-4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-ethanoneHCID 178526690HCID 178526690, compound

Product 1

HCID 178461578HCID 178461578, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Trans-4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexanol (118 mg, 0.39 mmol, prepared in accordance with Example 5) was placed under an inert atmosphere, dissolved in dry dimethylformamide (2 mL). A molar solution of lithium bis(trimethylsilyl)-amide (774 μL, 0.77 mmol) was added to the resulting mixture. The mixture was then stirred for 15 min at room temperature. Afterward, a solution of 2-chloro-1-[trans-2,5-dimethyl-4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-ethanone (130 mg, 0.39 mmol, prepared in accordance with Example 3) in tetrahydrofuran (1 mL) was added. The resulting mixture was stirred at room temperature until the conversion stopped. Next, the mixture was diluted with diethylether (10 mL). The mixture was then washed with water (5 mL), and then saturated aqueous sodium hydrogencarbonate (5 mL). The organic phase was collected, dried over magnesium sulfate, filtered, and concentrated under vacuum. The crude product isolated was purified by preparative HPLC. Following lyophilization of the fractions of interest, the desired product was isolated as a yellow solid (24 mg, 10% yield). The structure was confirmed using Protocol II-A. Calculated mass=603; observed mass=603; HPLC retention time=4.69 min.

Workup

  1. stirringThe resulting mixture was stirred at room temperature until the conversion
  2. washThe mixture was then washed with water (5 mL)
  3. customThe organic phase was collected
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude product isolated
  8. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-fb6208fceb0d420089993bb40e8948a5
Source dataset
uspto-grants-2013_10
Patent number
US08569495B2

Reaction notes

Loading…