2-Benzhydrylsulphinylacetic acid

Chemical Properties

Off-White to Pale Pink Solid

Uses

A metabolite of Modafinil, a central nervous system vigilance promoting agent, which possesses neuroprotective properties

Definition

ChEBI: Modafinil acid is a diarylmethane.

General Description

Modafinil acid is the major metabolite of modafinil, an analeptic drug sold under the brand names Provigil or Modavigil and approved by the US FDA for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness. Modafinil, a well known nootropic drug, is often used as a performance-enhancing drug in academics and sports.

Synthesis

General procedure for the synthesis of 2-diphenylmethylsulfinylacetic acid from 2-[(diphenylmethyl)thio]acetic acid: 1. 2-[(Diphenylmethyl)thio]acetic acid (416 g, 1.61 mol) was suspended in purified water (4160 mL) at 25 to 30°C. 2. a 30% sodium hydroxide solution was prepared by dissolving 70.90 g (1.77 mol) of sodium hydroxide flakes/granules in 235 mL of purified water at 25 to 30 °C and added to the above suspension over 15 min. 3. 50% hydrogen peroxide (142.5 g, 2.095 mol) was slowly added over a period of 5 to 6 hours under stirring, maintaining the reaction temperature between 25 and 35 °C. 4. continue stirring the reaction mixture at 25 to 35 °C for 15 to 20 hours until the reaction is complete (the residual amount of feedstock should be less than 0.5% area). 5. Upon completion of the reaction, toluene (1664 mL) is added and the mixture is stirred for 10 minutes. 6. With stirring, the reaction mixture is acidified with concentrated hydrochloric acid (250 mL) while maintaining the temperature between 25 and 30°C. The reaction mixture is then purified by adding toluene (1664 mL). 7. the resulting substance was continued to be stirred at 25 to 30 °C for 1 hour. 8. The precipitated product was collected by filtration, washed sequentially with water (3 x 832 mL) and toluene (416 mL), and then dried to give 416 g of 2-[(diphenylmethyl)sulfinyl]acetic acid as a white crystalline powder (yield: 94.17%, HPLC purity: 99.3%).

References

[1] Organic and Biomolecular Chemistry, 2017, vol. 15, # 12, p. 2647 - 2654
[2] Patent: WO2009/24863, 2009, A2. Location in patent: Page/Page column 14-15
[3] Patent: WO2009/24863, 2009, A2. Location in patent: Page/Page column 16-17
[4] Patent: WO2009/24863, 2009, A2. Location in patent: Page/Page column 16
[5] Patent: WO2009/24863, 2009, A2. Location in patent: Page/Page column 15-16