Formaldehyde → Diethyl P-[[[(4-methylphenyl)sulfonyl]oxy]methyl]phosphonate

HRID 1170965Notes

Reaction equation

HRID 1170965 reaction equation
[P:1]([O-:8])([O:5][CH2:6][CH3:7])[O:2][CH2:3][CH3:4].[CH2:9]=[O:10].[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>C(N(CC)CC)C.C1(C)C=CC=CC=1>[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17]([O:10][CH2:9][P:1](=[O:8])([O:5][CH2:6][CH3:7])[O:2][CH2:3][CH3:4])(=[O:19])=[O:18])=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 73974-Toluenesulfonyl chlorideHCID 3780918Diethylphosphite

Product 1

HCID 4193599Diethyl P-[[[(4-methylphenyl)sulfonyl]oxy]methyl]phosphonateYield 77.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8471TriethylamineSolvent2×

Procedure

A 12 L, 3-neck round bottom flask was equipped with a mechanical stirrer, condenser, thermometer and heating mantle. The flask was flushed with nitrogen and charged with diethyl phosphite (554 g, 3.77 mol), paraformaldehyde (142 g, 4.72 mol), toluene (2 L) and triethylamine (53 mL, 5.76 mol). The mixture was stirred at 85-90° for 2 h, then at reflux for 1 h. The resulting yellow solution was cooled to 4° C. (ice bath) and p-toluenesulfonyl chloride (718 g, 3.77 mol) was added. The condenser was replaced with an addition funnel and triethylamine (750 mL) was added slowly with stirring, maintaining the temperature <10° C. After the addition was complete (45 min.), the resulting mixture was stirred at ambient temperature for 14 h. The mixture was filtered and the filtercake was washed with toluene (2×250 mL). The combined filtrate and washings were washed with water (2×1 L, dried (MgSO4, 200 g), filtered through Celite 521, and concentrated under reduced pressure to provide 1004 g of a cloudy yellow oil (77.6%). 1H NMR (CDCl3): NMR (DMSO): 7.82 (d, J=8.2 Hz, 2H), 7.48 (d, J=8.2 Hz, 2H), 4.36 (d, J=9.6 Hz, 2H), 4.00 (m, 4H), 2.41 (s, 3H), 1.16 (m, 6H); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=40% EtOAc/hexanes, Rf=0.24.

Workup

  1. customA 12 L, 3-neck round bottom flask was equipped with a mechanical stirrer, condenser
  2. temperaturethermometer and heating mantle
  3. customThe flask was flushed with nitrogen
  4. temperatureat reflux for 1 h
  5. additionwas added
  6. customThe condenser was replaced with an addition funnel
  7. stirringwith stirring
  8. temperaturemaintaining the temperature <10° C
  9. additionAfter the addition
  10. custom(45 min.)
  11. stirringthe resulting mixture was stirred at ambient temperature for 14 h
  12. filtrationThe mixture was filtered
  13. washthe filtercake was washed with toluene (2×250 mL)
  14. washThe combined filtrate and washings were washed with water (2×1 L
  15. dry with materialdried (MgSO4, 200 g)
  16. filtrationfiltered through Celite 521
  17. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5901d0cd179c4872be0bf8110a39f636
Source dataset
uspto-grants-2010_11
Patent number
US07829552B2

Reaction notes

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