Toluene → Methyl (2s)-2-ethyl-2,3-dihydro-1-benzofuran-2-carboxylate

Temperatur

110 °C

To a solution of the acid from step 1 (4.0 g, ca. 20 mmol) in 1:4 DMF:toluene (100 mL.) was added 60% NaH in mineral oil (1.76 g, 44 mmol) in 3 portions. The reaction mixture was stirred at 110° C. under N2 for 4 hrs. The reaction was cooled to room temperature and poured into cold water (100 mL). The aqueous layer was washed with hexane (50 mL), acidified with 2 N aqueous HCl and extracted with ethyl acetate (3×50 mL). The extracts were washed with brine (50 mL), dried and concentrated. The residue was dissolved in 7:1 benzene:MeOH (80 mL) and treated with TMSCHN2 (1M in hexane) until gas evolution ceased. The reaction was concentrated and the residue was chromatographed on silica gel eluting with 85:15 hexane:ethylacetate to give methyl (2S)-2-ethyl-2,3-dihydro-benzofuran-2-carboxylate.

1. temperatureThe reaction was cooled to room temperature
2. washThe aqueous layer was washed with hexane (50 mL)
3. extractionextracted with ethyl acetate (3×50 mL)
4. washThe extracts were washed with brine (50 mL)
5. customdried
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in 7:1 benzene
8. additionMeOH (80 mL) and treated with TMSCHN2 (1M in hexane) until gas evolution
9. concentrationThe reaction was concentrated
10. customthe residue was chromatographed on silica gel eluting with 85:15 hexane

ORD-Eintrag

ord-f792c5cd496448999b4a07e13277c14c

Quelldatensatz

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07524882B2