Method for asymmetrically synthesizing (13R, 14S)-13-hydroxy-14-methylhexadecanoic acid
A methylhexadecane, asymmetric technology, applied in the field of new synthesis of 13-hydroxy-14-methylhexadecanoic acid, can solve the problems of chemical synthesis methods without literature reports
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Embodiment 1
[0033] Synthesis of (S,E)-3-methyl-4-hydroxy-7-tert-butyldiphenylsilyloxy-2-hepten-5-ynoic acid ethyl ester (3)
[0034] Under argon protection, at 0°C, a mixture of (R,R)-ProPhenol ligand (1.60g, 2.5 mmol, 0.25eq) and triphenylphosphine oxide (1.39g, 5mmol, 0.5eq) was added to a 250mL Schlenk reaction flask. Toluene (50mL) solution, stirred evenly. Slowly add 1-tert-butyldiphenylsiloxypropyne (8.80g, 30mmol, 3.0eq), then slowly inject Me 2 Zn solution (25 mL, 1.2M in toluene, 30mmol, 3.0eq). The mixture was warmed up to 25°C and stirred for 1.5h. Then the mixture was cooled to -5°C, and (E)-3-methyl-4-oxo-2-butenoic acid ethyl ester (2) (1.43g, 10mmol, 1.0eq) was slowly added with a syringe, and the reaction mixture was Stirring was continued at -5°C for 48 h. The reaction was quenched with water (20 mL), filtered and the organic layer was separated. The aqueous layer was extracted with ether (3 x 50 mL), and the organic layers were combined. The organic layer was washe...
Embodiment 2
[0038] Synthesis of (3S,4R)-3-methyl-7-tert-butyldiphenylsilyloxy-4-heptanolactone (4)
[0039] Under the protection of argon, the PtO 2 (0.20g, 0.88mmol, 0.16eq) was put into a 50mL Schlenk tube, and then evacuated and replaced with hydrogen. Under hydrogen atmosphere, anhydrous MeOH (10 mL) was added by syringe and stirred well. A solution of enynyl ester 3 (2.40 g, 5.5 mmol, 1.0 eq) in MeOH (5 mL) was added, stirring was continued for 24 h, and the reaction was stopped. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain the crude hydroxy ester.
[0040] The crude hydroxy ester was dissolved in MeOH (20 mL), transferred to a 100 mL three-neck flask, KOH (0.62 g, 11 mmol, 2.0 eq) was added at room temperature, the reaction was stirred for 2 h, and the reaction was stopped. The reaction solution was acidified with dilute hydrochloric acid (1M) to pH 5-7, extracted with EtOAc (3×50 mL), and the organic layers were combined. ...
Embodiment 3
[0042] Synthesis of (3S,4R)-3-methyl-7-tert-butyldiphenylsilyloxy-1,4-heptanediol (5)
[0043] Under argon protection, a solution of lactone 4 (0.67 g, 1.7 mmol, 1.0 eq) in anhydrous DCM (10 mL) was added to a 50 mL Schlenk tube. Cool down to -78°C, add DIBAL-H (2.1 mL, 1.2M solution in toluene, 2.55 mmol, 1.5 eq), and stir for 1 h. Within 2-3h, the reaction solution was slowly warmed to -40°C, and the reaction was stirred. With MeOH (5mL) and saturated NH 4 Aqueous Cl (10 mL) quenched the reaction. After filtration, the filtrate was separated, the aqueous layer was extracted with DCM (3×20 mL), and the organic layers were combined. The organic layer was washed with saturated brine (30 mL), washed with anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain the crude aldol condensation product.
[0044] The crude aldol condensation product was dissolved in MeOH (10 mL), and transferred to a 50 mL three-neck flask. Cool down to 0°C, slowly add NaBH 4 (0...
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