Hexane → (E)-2-Fluoro-3-(6-isopropyl-4,4-dimethyl-1-n-propyl-1,2,3,4-tetrahydro-quinolin-8-yl)-but-2-enal

Temperature

0 °C

To a solution of ethyl 4-(diethoxyphosphoryl)-3-methyl-but-2-enoate (210 mg, 0.80 mmol), 10 ml of anhydrous THF, and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (0.12 ml) under argon at −78° C. was slowly added a 1.6 M solution of n-butyl lithium and hexane (0.52 ml, 0.84 mmol). The resulting mixture was stirred at −78° C. for 30 minutes before a solution of (E)-3-(1-ethyl-6-isopropyl-4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-8-yl)-2-fluoro-but-2-enal (Intermediate 21, 87 mg, 0.27 mmol) and 3 ml THF was added by cannula. The resulting mixture was stirred at 0° C. for 1 h. The reaction was quenched with saturated NH4Cl, and the product was extracted with ethyl ether. The extract was washed with water, and brine, and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The residue was purified by column chromatography using 5% ethyl acetate in hexane to yield the title compound as a bright yellow oil.

1. additionwas added by cannula
2. customThe reaction was quenched with saturated NH4Cl
3. extractionthe product was extracted with ethyl ether
4. washThe extract was washed with water, and brine
5. dry with materialdried over Na2SO4
6. filtrationThe solution was filtered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography

ORD record

ord-2a40f2ded9c74ebe8ebbd971e9f9849c

Source dataset

uspto-grants-2004_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06734193B1