Dihydrolipoic Acid → 8-Acetylmercapto-6-mercaptooctanoic acid

Acetyl chloride (0.30 g, 3.8 mmol) in 4 mL of dry methylene chloride was added dropwise under a nitrogen atmosphere over 10 min to a stirred solution of 6,8-bismercaptooctanoic acid (0.80 g, 3.8 mmol) and triethylamine (1.16 g, 11.5 mmol) at 0. The solution was stirred at 0 a further 15 min then at room temperature for 2 hr. The solution was diluted to 75 mL with methylene chloride and extracted with 2×50 mL of 10% aqueous citric acid, then washed with 30 mL of saturated brine. The organic phase was dried (MgSO4), filtered and the solvent evaporated. The oil remaining was dissolved in 8 mL of 2-propanol and 8 mL of water added. The mixture was stirred under nitrogen at 40 for 4.5 hr. The solvent was evaporated in vacuo and the crude product mixture separated by column chromatography on silica gel first using ethyl acetate—hexane—acetic acid (100:100:1, v/v) as the eluting solvent, and then rechromatographed using hexane-ethyl acetate-acetic acid (150:100:1, v/v) as the solvent yielding 51 mg (5%) of pure 8-acetylmercapto-6-mercaptooctanoic acid as a colorless oil.

1. waitat room temperature for 2 hr
2. extractionextracted with 2×50 mL of 10% aqueous citric acid
3. washwashed with 30 mL of saturated brine
4. dry with materialThe organic phase was dried (MgSO4)
5. filtrationfiltered
6. customthe solvent evaporated
7. dissolutionThe oil remaining was dissolved in 8 mL of 2-propanol
8. addition8 mL of water added
9. stirringThe mixture was stirred under nitrogen at 40 for 4.5 hr
10. customThe solvent was evaporated in vacuo
11. customthe crude product mixture separated by column chromatography on silica gel first using ethyl acetate—hexane—acetic acid (100:100:1
12. customv/v) as the eluting solvent, and then rechromatographed

ORD record

ord-3656d07a3aa5453d8b6e30c0f13f2303

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06951887B2