Diethyl chlorophosphate → 1-(Diethoxyphosphorylmethylsulfonyl)-4-(4-methyl-2-pyridyl)piperazine

HRID 1775345Notes

Reaction equation

HRID 1775345 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10][CH2:9]2)[CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[P:28](Cl)([O:33][CH2:34][CH3:35])([O:30][CH2:31][CH3:32])=[O:29].[Cl-].[NH4+]>C1COCC1>[CH2:31]([O:30][P:28]([CH2:17][S:14]([N:11]1[CH2:12][CH2:13][N:8]([C:4]2[CH:3]=[C:2]([CH3:1])[CH:7]=[CH:6][N:5]=2)[CH2:9][CH2:10]1)(=[O:16])=[O:15])([O:33][CH2:34][CH3:35])=[O:29])[CH3:32]

Participants

6

Reactant 4

HCID 13139Diethyl chlorophosphateHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 898260101-(4-Methyl-2-pyridinyl)-4-(methylsulfonyl)piperazine

Product 1

HCID 898258041-(Diethoxyphosphorylmethylsulfonyl)-4-(4-methyl-2-pyridyl)piperazineYield 81.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

1-(4-Methyl-2-pyridyl)-4-methylsulfonyl-piperazine (1.16 g, 4.54 mmol) was dissolved in anhydrous THF (80 ml) and cooled under nitrogen to −78° C. Lithium bis(trimethylsilyl)amide (1M in THF, 14 ml, 14 mmol) was added dropwise and the mixture was stirred at −78° C. for one hour. Diethyl chlorophosphate (3.1 g, 18 mmol) was added dropwise and stirring was continued for one hour at −78° C., after which the mixture was allowed to reach room temperature over three hours. A saturated solution of ammonium chloride was added and the mixture was extracted with DCM (3×), the combined organic layers were dried (sodium sulfate), concentrated under reduced pressure and the residue was purified by column chromatography (silica, gradient from 0 to 6% methanol in DCM) to give 1.44 g of a light-brown oil (3.68 mmol, yield 81%) MS (ESI) m/z=392.1 [M+1]+.

Workup

  1. stirringstirring
  2. waitwas continued for one hour at −78° C.
  3. waitto reach room temperature over three hours
  4. extractionthe mixture was extracted with DCM (3×)
  5. dry with materialthe combined organic layers were dried (sodium sulfate)
  6. concentrationconcentrated under reduced pressure
  7. customthe residue was purified by column chromatography (silica, gradient from 0 to 6% methanol in DCM)

Sources & evidence

ORD record
ord-d3f1ae9dd82148ec9c7f3ef99e994bfc
Source dataset
uspto-grants-2016_02
Patent number
US09260441B2

Reaction notes

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