4-Hydroxy-3-methylsulfanylbenzoic acid → 4-Hydroxymethyl-2-methylsulfanylphenol

Temperature

60 °C

With ice-cooling, a solution of 7d (1.37 g; 7.4 mmol) in abs. tetrahydrofuran (THF; 15 ml) was added to a suspension of 95% pure LiAlH4 (0.55 g; 14 mmol) in absolute THF (10 ml) in a three-necked flask (which had been dried by heating and flushed with argon) such that there was only a moderate evolution of gas. After the addition had ended, cooling was removed and the reaction mixture was stirred at room temperature for 30 min and at 55-65° C. for a further 21 h. With ice-cooling, ice-water was added to the reaction mixture. The precipitate of Al(OH)3 was dissolved by adding 10% strength sulfuric acid, and the aqueous-acidic solution (pH 1) was extracted with diethyl ether (3×50 ml). The combined ethereal extract was extracted with 10% strength aqueous sodium hydroxide solution (2×25 ml). The combined sodium hydroxide solution was neutralized with 20% strength hydrochloric acid. The precipitate (8c) was filtered off, washed with H2O and dried. A further charge of 8c was obtained by extraction of the neutral aqueous solution with diethyl ether. The ethereal extract was washed with saturated NaCl solution, dried over Na2SO4 and concentrated: crystalline white solid.

1. temperatureWith ice-cooling
2. custom(which had been dried by heating and flushed with argon) such that there
3. additionAfter the addition
4. temperaturecooling
5. customwas removed
6. temperatureWith ice-cooling
7. additionice-water was added to the reaction mixture
8. dissolutionThe precipitate of Al(OH)3 was dissolved
9. additionby adding 10% strength sulfuric acid
10. extractionthe aqueous-acidic solution (pH 1) was extracted with diethyl ether (3×50 ml)
11. extractionThe combined ethereal extract
12. extractionwas extracted with 10% strength aqueous sodium hydroxide solution (2×25 ml)
13. filtrationThe precipitate (8c) was filtered off
14. washwashed with H2O
15. customdried
16. additionA further charge of 8c
17. customwas obtained by extraction of the neutral aqueous solution with diethyl ether
18. extractionThe ethereal extract
19. washwas washed with saturated NaCl solution
20. dry with materialdried over Na2SO4
21. concentrationconcentrated

ORD record

ord-73ddc196d0b84a0685d81cd6b7ee9789

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582660B2