Diethyl (tosyloxy)methylphosphonate Chemical Properties

Boiling point:

137°C/0.02mmHg(lit.)

Density 

1.255

refractive index 

1.4980 to 1.5020

storage temp. 

Inert atmosphere,2-8°C

solubility 

Chloroform (Sparingly), Dichloromethane, Ethyl Acetate, Methanol (Sparingly)

form 

Oil

color 

Clear Colourless to Pale Yellow

InChI

InChI=1S/C12H19O6PS/c1-4-16-19(13,17-5-2)10-18-20(14,15)12-8-6-11(3)7-9-12/h6-9H,4-5,10H2,1-3H3

InChIKey

UOEFFQWLRUBDME-UHFFFAOYSA-N

SMILES

P(COS(C1=CC=C(C)C=C1)(=O)=O)(=O)(OCC)OCC

CAS DataBase Reference

31618-90-3(CAS DataBase Reference)

Safety Information

Risk Statements 

36/37/38

Safety Statements 

36/37/39

HS Code 

29309090

Diethyl (tosyloxy)methylphosphonate Usage And Synthesis

Chemical Properties

Pale Yellow Oil

Uses

Diethyl (tosyloxy)methylphosphonate is an antiviral agent and a Tenofovir intermediate. Tenofovir is an acyclic phosphonate nucleotide analogue and reverse transcriptase inhibitor used as an anti-HIV agent.

Uses

Diethyl p-Toluenesulfonyloxymethylphosphonate is an antiviral agent and a Tenofovir (T018500) intermediate. Tenofovir is an acyclic phosphonate nucleotide analogue and reverse transcriptase inhibitor used as an anti-HIV agent.

Synthesis

The general procedure for the synthesis of diethyl p-toluenesulfonyl oxymethylphosphonate from diethyl hydroxymethylphosphonate and p-toluenesulfonyl chloride was as follows: first, diethyl hydroxymethylphosphonate (51 kg, 1107 mol) and diethyl phosphite (22 kg, 159.3 mol) were added to a glass autoclave, followed by the addition of anhydrous ethanol to promote mixing. After stirring until the mixture was homogeneous, paraformaldehyde (5.5 kg, 61.06 mol) and triethylamine (1.4 kg, 13.84 mol) were added to the kettle. The mixture was heated to 40°C for 0.5-1 hr for the reaction, and then warmed to 50-65°C to continue the reaction for 5 hr. Upon completion of the reaction, the mixture was cooled to 30-40°C, the solids were filtered by adding 0.3 kg of diatomaceous earth and washed with 2 kg of anhydrous ethanol. The filtrate and washings were combined and concentrated under reduced pressure at 55°C to remove ethanol. After concentration, toluene (18 kg, 195.35 mol) was added and concentration was continued until the ethanol was completely evaporated. After cooling the mixture to 30°C, it was further cooled to below -10°C and triethylamine (15.2 kg, 150.21 mol) was slowly added dropwise and p-toluenesulfonyl chloride (24.5 kg, 128.51 mol) was added in batches. The temperature was controlled at -3 to -10°C during the dropwise addition and stirring was continued for 1 hour after completion of the dropwise addition. The mixture was then heated to 19-25°C and the reaction was held for 2.5-3.5 hours. Upon completion of the reaction, 18 kg of water was added for washing and 5 kg of anhydrous sodium sulfate was added for drying for 6 hours. After filtration, the filtrate was concentrated under reduced pressure at 65°C to remove the solvent. The residue was a thickened form of diethyl p-toluenesulfonyl oxymethylphosphonate. Further distillation under reduced pressure at elevated temperature (152°C, 2-3 mmHg) afforded 30.14 kg of bouquets of diethyl p-toluenesulfonyl oxymethylphosphonate with ≥99% purity in 137% yield.

References

[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 11, p. 1477 - 1482
[2] Synlett, 2016, vol. 27, # 9, p. 1423 - 1427
[3] Patent: CN106699814, 2017, A. Location in patent: Paragraph 0017-0019
[4] Collection of Czechoslovak Chemical Communications, 1982, vol. 47, # 12, p. 3447 - 3463
[5] Patent: CN105541910, 2016, A. Location in patent: Paragraph 0031; 0032; 0034

Diethyl (tosyloxy)methylphosphonate(31618-90-3)Related Product Information

• Methylparaben
• Ethyl p-toluenesulfonate
• Tosyl cyanide
• Diethyl phthalate
• p-Toluenesulfonamide
• Acetonitrile
• Methanol
• Diethyl succinosuccinate
• Tosyl chloride
• Methyldiethoxyphosphine
• Mefenpyr-diethyl
• Diethyl carbonate
• Diethyl malonate
• TOLBUTAMIDE
• Ethyl propionylacetate
• Methyl acrylate
• Chloromethyl isopropyl carbonate
• Tenofovir