Nordihydroguaretic acid → 1,4-bis{3,4-bis(2-methyl-thiazol-4-yl-methoxy)phenyl}-2,3-dimethyl-(2R,3S)-butane

Temperatur

0 °C

To an ice-cooled solution of NDGA (1.50 g, 4.96 mol) in DMF (50 mL) was added 60% suspension of sodium hydride in paraffin (1.98 g=1.19 g NaH, 49.6 mmol, 10 mole equiv.). The mixture was stirred at 0° C. for 30 min. and at room temperature for 30 min. Then a solution of 4-chloromethyl-2-methylthiazole (5.86 g, 39.69 mmol, 8.0 mole equiv.) in DMF (20 mL) was added and the reaction mixture was allowed to stir for 16 h at room temperature. The reaction mixture was added to the saturated aqueous ammonium chloride (300 mL) and ether (600 mL). After shaking, the organic layer was separated, and the aqueous layer was extracted with ether (2×200 mL). The combined organic layer and extracts were washed with water (100 mL), brine (100 mL), and dried over anhydrous sodium sulfate and concentrated to dryness under reduced vacuum (30-40 mm Hg) at 25° C. The residue was dissolved in a minimum amount of dichloromethane and purified by silica gel flash chromatographic column using hexane:ethyl acetate (50:50 to 0:100) as eluant to give expected product as white solid (1.56 g, 42.09% yield). It was further purified by crystallization from acetate-hexane.

1. stirringto stir for 16 h at room temperature
2. stirringAfter shaking
3. customthe organic layer was separated
4. extractionthe aqueous layer was extracted with ether (2×200 mL)
5. washThe combined organic layer and extracts were washed with water (100 mL), brine (100 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated to dryness under reduced vacuum (30-40 mm Hg) at 25° C
8. dissolutionThe residue was dissolved in a minimum amount of dichloromethane
9. custompurified by silica gel flash chromatographic column

ORD-Eintrag

ord-12238994eecd46bcbe06be08d7e07338

Quelldatensatz

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08178527B2