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

HRID 511528

Reaction equation

HRID 511528 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>[CH3:1][O:2][C:3]1[N:4]=[C:5]([CH2:13][P:14](=[O:21])([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17])[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10]

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:EtOAc1:1). 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:EtOAc1:1)
  7. washThe slower eluting regioisomer
  8. customwas collected

Sources & evidence

ORD record
ord-3e15dcb503f74ebdb062b7c0cbe04f65
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Linked notes

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