Sodium hydride → Tetramethyl 1-(4-nitrobenzyl)methylenebisphosphonate

HRID 1841903Notes

Reaction equation

HRID 1841903 reaction equation
[H-].[Na+].[CH2:3]([P:10](=[O:15])([O:13][CH3:14])[O:11][CH3:12])[P:4](=[O:9])([O:7][CH3:8])[O:5][CH3:6].[N+:16]([C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Br)=[CH:21][CH:20]=1)([O-:18])=[O:17]>CN(C=O)C.C1COCC1>[N+:16]([C:19]1[CH:26]=[CH:25][C:22]([CH2:23][CH:3]([P:4](=[O:9])([O:7][CH3:8])[O:5][CH3:6])[P:10](=[O:15])([O:11][CH3:12])[O:13][CH3:14])=[CH:21][CH:20]=1)([O-:18])=[O:17]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 660114-Nitrobenzyl bromideHCID 519206Tetramethyl methylenediphosphonate

Product 1

HCID 86624879Tetramethyl 1-(4-nitrobenzyl)methylenebisphosphonateYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (1.02 g, 25.4 mmol) was added in portions to a stirring solution of tetramethyl methylenebisphosphonate in DMF (40 mL). After 30 min a solution of 4-nitrobenzylbromide (5.00 g, 23.1 mmol) in THF (5 mL) was added and the resulting mixture was stirred at room temperature for 4.5 hr. The reaction was quenched by the addition of saturated aqueous NH4Cl (20 mL). After the addition of water (100 mL) the product was extracted with EtOAc and the combined organics were washed with brine, dried over MgSO4, filtered and concentrated at reduced pressure. The crude product was purified by silica gel chromatography (0% to 10% MeOH in EtOAc) resulting in 12 as a colorless solid (2.55 g, 30%). 1H NMR (400 MHz, CDCl3) δ 2.65 (tt, J=6.5, 23.8, 1H), 3.31 (dt, J=6.5, 16.5, 2H), 3.73 (d, J=7.0, 6H), 3.75 (d, J=7.0, 6H), 7.42 (d, J=8.9, 2H), 8.15 (d, J=8.9, 2H).

Workup

  1. customThe reaction was quenched by the addition of saturated aqueous NH4Cl (20 mL)
  2. additionAfter the addition of water (100 mL) the product
  3. extractionwas extracted with EtOAc
  4. washthe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customThe crude product was purified by silica gel chromatography (0% to 10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-eb6233abc20646c9b384e7844f1e8551
Source dataset
uspto-grants-2015_02
Patent number
US08946144B2

Reaction notes

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