Iodine → Propanoic acid, 2-[[(4-methoxyphenyl)methyl]thio]-2-methyl-

Sodium methoxide (81 g, 1.5 mol) was added to 50 ml methanol and 375 ml freshly distilled tetrahydrofuran. The slurry was stirred in an ice bath and 4-methoxybenzylmercaptan (80 g, 0.52 mol) was added slowly. The cloudy orange solution was stirred at room temperature for 1.25 hours, 2-bromo-2-methylproprionic acid (83.5 g, 0.5 mol) was dissolved in 200 ml tetrahydrofuran and added to the mixture. The thick slurry was stirred at reflux for 70 h, then cooled to room temperature. Iodine crystals were added until a red colour persisted. The mixture was dissolved in 2000 ml 0.5M sodium hydroxide solution, and washed with 2×1000 ml ether. The aqueous layer was acidified and extracted with 2×1000 ml ether. The ether layer was washed with 2×1000 ml saturated sodium chloride solution, dried over sodium sulphate, and filtered. The solvent was removed by rotary evaporation to yield an orange solid. This was recrystallised from ethyl acetate to give 70.3 g of the desired product (59% yield) as white crystals. 1H NMR (60 MHz, CDCl3): 1.57 (s, 6H), 3.73 (s, 3H), 3.83 (s, 2H), 6.5-7.5 (m, 4H), 10.90 (brs, 1H) ppm. TLC (50% ether/hexane) Rf 0.30.

1. stirringThe cloudy orange solution was stirred at room temperature for 1.25 hours
2. additionadded to the mixture
3. stirringThe thick slurry was stirred
4. temperatureat reflux for 70 h
5. washwashed with 2×1000 ml ether
6. extractionextracted with 2×1000 ml ether
7. washThe ether layer was washed with 2×1000 ml saturated sodium chloride solution
8. dry with materialdried over sodium sulphate
9. filtrationfiltered
10. customThe solvent was removed by rotary evaporation
11. customto yield an orange solid
12. customThis was recrystallised from ethyl acetate

ORD record

ord-1641d80ef2ef4fd58d7acacb09ec97e6

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05690904