Formaldehyde → Dimethyl 4-methylaminobenzylphosphonate

HRID 1079315Notes

Reaction equation

HRID 1079315 reaction equation
[NH2:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9])=[CH:4][CH:3]=1.[CH2:15]=O.C[O-].[Na+].[BH4-].[Na+]>CO>[CH3:15][NH:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][P:7](=[O:12])([O:8][CH3:9])[O:10][CH3:11])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 10942334Sodium MethoxideHCID 12843961Dimethyl [(4-aminophenyl)methyl]phosphonate

Product 1

HCID 18928077Dimethyl 4-methylaminobenzylphosphonateYield 13%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dimethyl 4-aminobenzylphosphonate (21.5 g) and then paraformaldehyde (80%, 5.3 g) were added at room temperature to a solution of sodium methoxide in methanol (prepared from 27 g of sodium and 250 ml of methanol). After this mixture was stirred at room temperature for 15 hours, sodium borohydride (3.8 g) was added, and the mixture was heated for 1.5 hours while refluxing. The reaction mixture was concentrated under reduced pressure and then the residue was treated with 1NKOH (500 ml) and extracted with chloroform. The chloroform layer was washed with water and dried (MgSO4), after which the solvent was distilled off. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-chloroform-methanol (25:25:1, v/v) to yield dimethyl 4-methylaminobenzylphosphonate (2.9 g, 13%) as an oily substance. NMR(δ ppm in CDCl3): 2.55(1H,broad s), 2.82(3H,s), 3.07(2H,d,J=21 Hz), 3.63(3H,s), 3.69(3H,s), 6.57(2H,dd,J=9&1 Hz), 7.11(2H,dd,J =9&3 Hz)

Workup

  1. temperaturethe mixture was heated for 1.5 hours
  2. temperaturewhile refluxing
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was treated with 1NKOH (500 ml)
  5. extractionextracted with chloroform
  6. washThe chloroform layer was washed with water
  7. dry with materialdried (MgSO4)
  8. distillationafter which the solvent was distilled off
  9. washeluted with ethyl acetate-chloroform-methanol (25:25:1

Sources & evidence

ORD record
ord-fdc6df87e4cc4beda357a7499944f946
Source dataset
uspto-grants-1996_12
Patent number
US05580863

Reaction notes

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