2,3-Dihydroxybutanedioic Acid → HCID 10856043, compound

Temperature

-20 °C

A solution of L-(+)-diethyl tartrate (766 mg, 3.70 mmol) in 1HPLC system: Zorbax SB-C18 25 cm column, 90:10/ACN:water eluent, 220 nm, 1.0 mL/min. The reaction was considered complete when less than or equal to 3% area 21 remained. 2Silica gel was used as the drying agent because it also removed some baseline impurities. methylene chloride (25 ml) over activated 4 Å powdered molecular sieves (3.0 g) was cooled to -20° C. and Ti(O-i-Pr)4 (0.917 ml, 3.08 mmol) was added. After the mixture was stirred for 10 min, a solution of 15 (5.00 g, 30.8 mmol) in toluene (5.0 ml) was added maintaining the temperature below -18° C. The reaction was stirred at -20° C. for 35 min and tert-butyl hydroperoxide in decane (14.54 ml, 77.05 mmol, 5.3 M, stored over pellet 3 Å molecular sieves for 30 min prior to use) was added over 20 min, maintaining the temperature below -18° C. The reaction was allowed to stir at -20° C. until HPLC analysis3 showed >98% conversion (2.5 h). The reaction was allowed to warm to -5° C. and was poured into a mixture comprised of FeSO4 7H2O (13.2 g), tartaric acid (4.0 g), and 40 ml of water at 2° C. After stirring for 20 min the brown mixture was filtered through celite, washing with toluene. The filtrate layers were sparated and the aqueous was washed with toluene (2×20 ml). The combined organics were poured into a mixture containing NaCl (2.5 g), NaOH (15 g), and 40 ml of water at 0° C. After stirring for 1 h, the layers were separated and the aqueous layer was extracted with toluene (2×20 ml). The combined organics were dried (MgSO4), filtered, and concentrated in vacuo to give a yellow oil. Chromatography (165 g of flash SiO2) eluting with ethyl acetate:hexanes (2:1) provided 4.46 g (81%) of 16 as a colorless oil. 3 HPLC conditions: Chromsil C-18 column (1×25 cm), isocratic elution (50% acetonitrile/50% water both with 0.5% TFA), 1 ml/min flow rate for 20 min with UV detection ata 206 nm.

1. customalso removed some baseline impurities
2. temperaturemaintaining the temperature below -18° C
3. stirringThe reaction was stirred at -20° C. for 35 min
4. additionwas added over 20 min
5. temperaturemaintaining the temperature below -18° C
6. stirringto stir at -20° C. until HPLC
7. custom>98% conversion (2.5 h)
8. temperatureto warm to -5° C.
9. additionwas poured into a mixture
10. stirringAfter stirring for 20 min the brown mixture
11. filtrationwas filtered through celite
12. washwashing with toluene
13. washthe aqueous was washed with toluene (2×20 ml)
14. additionThe combined organics were poured into a mixture
15. additioncontaining NaCl (2.5 g), NaOH (15 g), and 40 ml of water at 0° C
16. stirringAfter stirring for 1 h
17. customthe layers were separated
18. extractionthe aqueous layer was extracted with toluene (2×20 ml)
19. dry with materialThe combined organics were dried (MgSO4)
20. filtrationfiltered
21. concentrationconcentrated in vacuo
22. customto give a yellow oil
23. washChromatography (165 g of flash SiO2) eluting with ethyl acetate:hexanes (2:1)

ORD record

ord-b17f8fde59244a4cb5a6847056583af6

Source dataset

uspto-grants-2000_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06020512