4-Toluenesulfonyl chloride → (R)-Methyl 2-(p-Tolyloxy)propanoate

Temperatur

-5 °C

Methyl (R)-(+)-lactate (3.33 g) and acetonitrile (16.7 ml) were charged to a flask and the resulting solution cooled to −5° C. Triethylamine (4.9 ml) was added. Triethylamine hydrochloride (0.31 g) was added. A solution of para-toluenesulfonyl chloride (5.8 g) dissolved in acetonitrile (16.7 ml) was added dropwise to the reaction mixture (over 40 mins), maintaining the temperature below 5° C. After complete addition a precipitate formed which was filtered. The filtrate was diluted further with acetonitrile (55 ml), to give (2R)-2-(4-methylphenoxy)-propanoic acid, methyl ester. The solution was treated with potassium carbonate (5 g) and 5-chloro-2-hydroxy benzaldehyde. The reaction mixture was heated at 50° C. for 32 h, then cooled to 20° C., diluted with water (100 ml) and extracted with tert-butyl methyl ether (250 ml). The organic phase was washed (brine), dried (MgSO4) and concentrated in vacuo. The residue was purified by chromatography (silica, 5-20% EtOAc/hexane as eluent) to give the sub-title compound (5.3 g).

1. additionwas added dropwise to the reaction mixture (over 40 mins)
2. temperaturemaintaining the temperature below 5° C
3. additionAfter complete addition a precipitate
4. customformed which
5. filtrationwas filtered
6. additionThe filtrate was diluted further with acetonitrile (55 ml)

ORD-Eintrag

ord-6ac9adf0a9a94a1e9907063836da2b55

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08524715B2