Tetraisopropyl methylenediphosphonate → Dihydro-1-pyrindine-6,6-diphosphonic acid tetraethyl ester

HRID 963639Notes

Reaction equation

HRID 963639 reaction equation
[H-].[K+].[CH:3]([O:6][P:7]([CH2:13][P:14]([O:20][CH:21]([CH3:23])C)(=[O:19])[O:15][CH:16]([CH3:18])C)(=[O:12])[O:8][CH:9]([CH3:11])C)([CH3:5])C.Cl[CH2:25][C:26]1[C:31]([CH2:32]Cl)=[CH:30][CH:29]=[CH:28][N:27]=1>CS(C)=O>[CH2:21]([O:20][P:14]([C:13]1([P:7]([O:6][CH2:3][CH3:5])(=[O:12])[O:8][CH2:9][CH3:11])[CH:25]=[C:26]2[C:31]([CH:30]=[CH:29][CH2:28][NH:27]2)=[CH:32]1)(=[O:19])[O:15][CH2:16][CH3:18])[CH3:23]

Participants

5

Reactant 3

HCID 74266Tetraisopropyl methylenediphosphonateHCID 82127Potassium hydrideHCID 145187502,3-Bis(chloromethyl)pyridine

Product 1

HCID 86752757Dihydro-1-pyrindine-6,6-diphosphonic acid tetraethyl ester

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent3×

Procedure

To an ice bath chilled solution of 35% potassium hydride in mineral oil (5.2 g; 0.045 moles) stirring under argon in 70 ml of DMSO (dry) is added a solution of tetraisopropylmethanediphosphonate (7.82 g; 0.023 moles) in 30 ml of DMSO. On completion of a dropwise addition, the resulting solution is stirred at room temperature for one hour. A solution of 2,3-bis(chloromethyl)pyridine (4.0 g; 0.023 mole) (crude product as isolated by K. Tsuda et.al., Chem Pharm Bull., 1, (1953), 142) in 15 ml of DMSO is slowly added and the reaction mixture is then heated at 90° C. for 1 hour. After cooling, the DMSO is removed under vacuum. 2.1 g (21%) of the desired product is purified via flash chromatography using a 5-15% ethanol in methylene chloride gradient on silica gel.

Workup

  1. additionOn completion of a dropwise addition
  2. temperaturethe reaction mixture is then heated at 90° C. for 1 hour
  3. temperatureAfter cooling
  4. customthe DMSO is removed under vacuum
  5. custom2.1 g (21%) of the desired product is purified via flash chromatography

Sources & evidence

ORD record
ord-3cd9155cb6d546df9855b03fe6ca22b7
Source dataset
uspto-grants-1998_06
Patent number
US05763611

Reaction notes

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