Réaction #721033

Équation de réaction

Potassium tert-butoxide

[6-[3-(3-chloro-5-fluoro-6-methoxy-quinolin-4-yl)-2,3-dihydroxy-propyl]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester

n-hexane

racemic-2-di-tert-butylphosphino-1,1′-binaphthyl

→

(3R,6S)-[6-(9-fluoro-1-hydroxy-8-methoxy-1,2-dihydro-furo[2,3-c]quinolin-2-ylmethyl)-tetrahydro-pyran-3-yl]-carbamic acid tert-butyl ester

Rendement 56.3%

Solvants

dioxane

ethyl acetate

Conditions de réaction

Traitement

1. 1
   Températurethe reaction mixture is cooled down to room temperature
2. 2
   Filtrationfiltered through decalite
3. 3
   ConcentrationThe filtrate is concentrated
4. 4
   Autrethe crude product is purified by column chromatography (silica gel, eluent

Mode opératoire

Potassium tert-butoxide (231 mg, 2.06 mmol, 2.0 eq) is added at room temperature to a stirred solution of (3R,6S)-{[6-[3-(3-chloro-5-fluoro-6-methoxy-quinolin-4-yl)-2,3-dihydroxy-propyl]-tetrahydro-pyran-3-yl}-carbamic acid tert-butyl ester (500 mg, 1.03 mmol, 1.0 eq) in dioxane (50 mL), followed by palladium(II) acetate (93 mg, 0.41 mmol, 0.4 eq) and racemic-2-di-tert-butylphosphino-1,1′-binaphthyl (164 mg, 0.41 mmol, 0.4 eq). After 16 hours stirring at 100° C., the reaction mixture is cooled down to room temperature and filtered through decalite. The filtrate is concentrated and the crude product is purified by column chromatography (silica gel, eluent: n-hexane:ethyl acetate, 5:1, v/v) to afford (3R,6S)-[6-(9-fluoro-1-hydroxy-8-methoxy-1,2-dihydro-furo[2,3-c]quinolin-2-ylmethyl)-tetrahydro-pyran-3-yl]-carbamic acid tert-butyl ester as a yellow solid (260 mg, 56% yield).

Source