CID 406 → Phosphonic acid

HRID 2081783Notes

Reaction equation

HRID 2081783 reaction equation
[NH2:1][CH2:2][P:3](=[O:6])([OH:5])[OH:4].[C:7](Cl)(C1C=CC=CC=1)([C:14]1C=CC=CC=1)[C:8]1C=CC=C[CH:9]=1.P(=O)([O-])[O-].C([NH+](CC)CC)C.CNC.N=C=N.C1CCC(N=C=NC2CCCCC2)CC1.Cl.[NH+]1C=CC=CC=1>C(Cl)(Cl)Cl.O.CO.C(N(CC)CC)C>[PH:3](=[O:4])([OH:6])[OH:5].[NH+:1]1[CH:2]=[CH:9][CH:8]=[CH:7][CH:14]=1

Participants

14

Reactant 8

HCID 406CID 406HCID 674DimethylamineHCID 6456Trityl chlorideHCID 10868DicyclohexylcarbodiimideHCID 14017(Aminomethyl)phosphonic acidHCID 160435CarbodiimideHCID 1385867TriethylammoniumHCID 21584435Pyridinium hydrochloride

Product 2

HCID 407Phosphonic acidHCID 4989215Pyridinium

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 8471TriethylamineSolvent

Procedure

Aminomethylphosphonic acid (Aldrich Chem. Co.) is reacted with trityl chloride in the presence of triethylamine. The dianionic phosphonate product, where the counter ions are triethylammonium, is mixed with an excess of reagent suitable for adding the desired pendant X moiety (e.g., addition of methanol gives X=methoxy, and addition of dimethylamine gives X=N(CH3)2) and then a carbodiimide, such as dicyclohexylcarboiimide (DCC), is added. The resultant monoanionic product is shaken with a mixture of water and chloroform containing pyridinium hydrochloride. This procedure gives a monoionic phosphonic acid having a pyridinium counter ion. This product is added to chloroform containing N4-Benzoylcytidine-2',3'-phenylboronate and DCC is added. The product is dried and chromatographed on silica using methanol/chloroform mixtures. The pure product is next treated with 1,3-dihydroxypropane to give Structure 2 of FIG. 12, and a portion is further treated with acetic acid in trifluoroethanol to give Structure 1.

Workup

  1. additionis mixed with an excess of reagent suitable
  2. additionfor adding the desired

Sources & evidence

ORD record
ord-741a5158a6fc4b7591eee9b11513cc0e
Source dataset
uspto-grants-1993_02
Patent number
US05185444

Reaction notes

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