Hexane → Ethyl (2E,4E,6E)-7-(3-ethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-6-fluoro-3-methylnona-2,4,6-trienoate

Temperature

0 °C

A solution of n-butyl lithium and hexane (16.4 mL, 1.6 M, 26.2 mmol) was added over 20 minutes down the side of the flask into a stirring solution of ethyl 4-(diethoxyphosphoryl)-3-methylbut-2-enoate (6.92 g, 26.2 mmol referenced in text in THF (75 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) (1.11 mL, available from Aldrich Chemical Co.) at −78° C. After 30 min, the mixture was treated with a solution of (E)-3-(3-ethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-fluoropent-2-enal (Intermediate 5, 3.55 g, 8.02 mmol) in THF (25 mL). The resulting solution was stirred for 2 h at 0° C. and then cooled again to −78° C. The reaction was quenched at −78° C. by adding saturated aqueous ammonium chloride. The solution was warmed to room temperature, and the products were extracted three times with ether. The combined organic layers were washed with water, brine and dried over magnesium sulfate. The solvent was removed in vacuo to give the title compound after purification by silica gel chromatography using a 94:6 mixture of hexane:ethyl acetate.

1. customat −78° C
2. temperaturecooled again to −78° C
3. customThe reaction was quenched at −78° C.
4. additionby adding saturated aqueous ammonium chloride
5. temperatureThe solution was warmed to room temperature
6. extractionthe products were extracted three times with ether
7. washThe combined organic layers were washed with water, brine
8. dry with materialdried over magnesium sulfate
9. customThe solvent was removed in vacuo

ORD record

ord-fe39df250e744d29be50f91a520b59ff

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07019034B2