Dimethylformamide → HCID 59310819, compound

HRID 1841906Notes

Reaction equation

HRID 1841906 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+].C(Cl)Cl.C[N:28](C=O)C>C1COCC1>[NH2:28][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]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 11163481HCID 11163481, compound

Product 1

HCID 59310819HCID 59310819, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of bisphosphonate 23 (2.0 g, 5.95 mmol) in DMF (6 mL) was added NaH (60% dispersion in mineral oil, 254 mg, 6.35 mmol) portionwise. The solution was stirred for 45 min at room temperature and added to a solution of O-(diphenylphophinyl)hydroxylamine (1.35 g, 5.77 mmol) in THF (40 mL), cooled in a dry ice/acetone bath. The resulting mixture was stirred for 10 min at the same temperature then 18 h at room temperature. CH2Cl2 (40 mL) was added, the solids were removed by filtration and washed with several portions of CH2Cl2. The combined filtrates were concentrated in vacuo and purified by flash chromatography on silica gel using a gradient of 0-5% MeOH/EtOAc to provide aminobisphosphonate 24 as a clear yellow oil (1.24 g, 3.53 mmol, 59%). 1H NMR (400 MHz, CDCl3) δ 1.69 (bs, 2H), 3.52 (t, J=20.8 Hz, 1H), 4.64-4.67 (m, 8H), 5.24-5.27 (m, 4H), 5.36-5.42 (m, 4H), 5.92-6.02 (m, 4H).

Workup

  1. temperaturecooled in a dry ice/acetone bath
  2. stirringThe resulting mixture was stirred for 10 min at the same temperature
  3. custom18 h
  4. customat room temperature
  5. customthe solids were removed by filtration
  6. washwashed with several portions of CH2Cl2
  7. concentrationThe combined filtrates were concentrated in vacuo
  8. custompurified by flash chromatography on silica gel using a gradient of 0-5% MeOH/EtOAc

Sources & evidence

ORD record
ord-2db74a01b1b54cb68950606e6ed70324
Source dataset
uspto-grants-2015_02
Patent number
US08946144B2

Reaction notes

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