Phosphonic acid, P-(chloromethyl)-, diethyl ester → Diethyl[(6-methoxy-5-nitropyridin-2-yl)methyl]phosphonate

HRID 1948097Notes

Reaction equation

HRID 1948097 reaction equation
[CH3:1][O:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][N:4]=1.Cl[CH2:13][P:14](=[O:21])([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17].CC(C)([O-])C.[K+]>CS(C)=O>[CH2:16]([O:15][P:14]([CH2:13][C:5]1[CH:6]=[CH:7][C:8]([N+:9]([O-:11])=[O:10])=[C:3]([O:2][CH3:1])[N:4]=1)(=[O:21])[O:18][CH2:19][CH3:20])[CH3:17]

Participants

5

Reactant 3

HCID 76633Phosphonic acid, P-(chloromethyl)-, diethyl esterHCID 2532192-Methoxy-3-nitropyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 86654057Diethyl[(6-methoxy-5-nitropyridin-2-yl)methyl]phosphonateYield 5.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

A solution of 2-methoxy-3-nitropyridine (6.92 g, 44.9 mmol) and diethyl chloromethylphosphonate (7.00 mL, 44.9 mmol) in 40 mL DMSO was added drop wise to a stirred mixture of potassium tert-butoxide (15.1 g, 134.6 mmol) and 40 mL DMSO. The mixture was stirred at room temperature for 30 minutes, after which, it was poured into a 1N HCl/ice mixture and extracted with methylene chloride. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography (DCM:EtOAc 1:1). The slower eluting regioisomer was collected and confirmed to be the desired product (750 mg, 5.5% yield). MS (ES+): m/z 305.16 (100) [MH−]; HPLC: tR=1.16 min (UPLC, Analytical).

Workup

  1. extractionextracted with methylene chloride
  2. washThe combined organic layers were washed with water, brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by column chromatography (DCM:EtOAc 1:1)
  7. washThe slower eluting regioisomer
  8. customwas collected

Sources & evidence

ORD record
ord-7b9076b586e2403ebbd6a9821df68730
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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