Sodium hydride → HCID 86641293, compound

HRID 1841907Notes

Reaction equation

HRID 1841907 reaction equation
[CH2:1]([P:12](=[O:21])([O:17][CH2:18][CH:19]=[CH2:20])[O:13][CH2:14][CH:15]=[CH2:16])[P:2](=[O:11])([O:7][CH2:8][CH:9]=[CH2:10])[O:3][CH2:4][CH:5]=[CH2:6].[H-].[Na+].[N+:24]([C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1)([O-:26])=[O:25].[NH4+].[Cl-]>CN(C=O)C.C1COCC1.O>[N+:24]([C:27]1[CH:34]=[CH:33][C:30]([CH2:31][CH:1]([P:2](=[O:11])([O:7][CH2:8][CH:9]=[CH2:10])[O:3][CH2:4][CH:5]=[CH2:6])[P:12](=[O:21])([O:13][CH2:14][CH:15]=[CH2:16])[O:17][CH2:18][CH:19]=[CH2:20])=[CH:29][CH:28]=1)([O-:26])=[O:25]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 660114-Nitrobenzyl bromideHCID 11163481HCID 11163481, compound

Product 1

HCID 86641293HCID 86641293, compoundYield 39.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of bisphosphonate 23 (8.02 g, 23.9 mmol) in DMF (24 mL) was added NaH (60% dispersion in mineral oil, 954 mg, 23.9 mmol) portionwise and the solution was stirred for 1.5 h at room temperature. A solution of p-nitrobenzyl bromide (7.75 g, 35.9 mmol) in THF (32 mL) was added and the mixture was stirred for 3 h at room temperature. It was then poured into a mixture of saturated aqueous NH4Cl solution and water and extracted with CH2Cl2 (3×). The combined organic layers were washed with saturated brine once, dried over MgSO4 and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using a gradient of 0-50% EtOAc in CH2Cl2 as eluant to provide nitrobenzyl bisphosphonate 26 as a clear yellow oil (4.42 g, 9.38 mmol, 39%). 1H NMR (400 MHz, CDCl3) δ 2.73 (tt, J=23.8, 6.5 Hz, 1H), 3.37 (dt, J=16.4, 6.5 Hz, 2H), 4.51-4.61 (m, 8H), 5.21-5.25 (m, 4H), 5.29-5.35 (m, 4H), 5.83-5.93 (m, 4H), 7.44 (d, J=8.8 Hz, 2H), 8.14 (d, J=8.8 Hz, 2H).

Workup

  1. stirringthe mixture was stirred for 3 h at room temperature
  2. extractionextracted with CH2Cl2 (3×)
  3. washThe combined organic layers were washed with saturated brine once
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel using a gradient of 0-50% EtOAc in CH2Cl2 as eluant

Sources & evidence

ORD record
ord-d2d99db962944f0babb5cfba08c90e55
Source dataset
uspto-grants-2015_02
Patent number
US08946144B2

Reaction notes

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