Isoprene → (R)-((S)-4,4-dimethyl-2-oxotetrahydrofuran-3-yl) 4-methylcyclohex-3-enecarboxylate

(S)-4,4-dimethyl-2-oxotetrahydrofuran-3-ylacrylate 501 (2.05 g, 11.1 mmol) in dichloromethane (17.5 mL) and hexanes (2.5 mL) was cooled to −10° C. and treated with titanium tetrachloride (2.2 mL, 1 M in dichloromethane, 2.2 mmol). The yellow solution was stirred for 15 minutes and treated with isoprene (1.67 mL, 16.7 mmol) dropwise over 5 minutes. After stirring for 2 hours, an additional portion of isoprene (1.67 mL, 16.7 mmol) was added and the reaction mixture was stirred at −10 to 0° C. for 3.5 hours. The reaction mixture was quenched with ammonium chloride (sat. aq.). Water and ethyl acetate:hexanes (1:1) were added. The organic layer was separated and the aqueous layer was extracted again with ethyl acetate:hexanes (1:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (10-50% EtOAc:Hex, 80 g column) to afford 1.30 g (46% yield) of (R)—((S)-4,4-dimethyl-2-oxotetrahydrofuran-3-yl) 4-methylcyclohex-3-enecarboxylate 502 as a clear oil.

1. stirringAfter stirring for 2 hours
2. stirringthe reaction mixture was stirred at −10 to 0° C. for 3.5 hours
3. customThe reaction mixture was quenched with ammonium chloride (sat. aq.)
4. additionWater and ethyl acetate:hexanes (1:1) were added
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted again with ethyl acetate:hexanes (1:1)
7. dry with materialThe combined organic layers were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography (10-50% EtOAc:Hex, 80 g column)

ORD record

ord-6119019f46f647a2a5d1cab2287c897d

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09393256B2