Methoxymethyl-triphenylphosphonium chloride → 4-(3-Fluoro-4-methylphenyl)-3,3-dimethylbutanal

Lithium bis(trimethylsilyl)amide solution (55 ml, 55 mmol, 1M in THF) was added to a mixture methoxy methyl triphenyl phosphonium chloride (18.9 g, 55 mmol) in 65 ml THF dropwise at 0° C. and stirred for 15 min and it was added to a mixture of the product of STEP 3 (7.3 g, 34.7 mmol ) in 35 ml THF dropwise at 0° C. After 5 min, the reaction was quenched with H2O. The product was extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with H2O, brine, dried with Na0.2SO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=5/95) to give a yellow liquid in 6.3 g. It was dissolved in 100 ml THF and 100 ml 2N HCl. The reaction was heated at reflux for 30 min and cooled to room temperature. THF was evaporated. The product was extracted with ethyl acetate and washed H2O. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried with Na2SO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=15/85) to yield a colorless oil in 3.8 g. NMR spectra of the product were consistent for the proposed structure.

1. waitAfter 5 min
2. customthe reaction was quenched with H2O
3. extractionThe product was extracted with ethyl acetate
4. extractionThe aqueous layer was extracted with ethyl acetate
5. washThe combined organic layer was washed with H2O, brine
6. customdried with Na0.2SO4
7. concentrationconcentrated
8. customThe residue was purified by chromatography (on silica gel, ethyl acetate/hexane=5/95)
9. customto give a yellow liquid in 6.3 g
10. temperatureThe reaction was heated
11. temperatureat reflux for 30 min
12. customTHF was evaporated
13. extractionThe product was extracted with ethyl acetate
14. washwashed H2O
15. extractionThe aqueous layer was extracted with ethyl acetate
16. washThe combined organic layer was washed with brine
17. dry with materialdried with Na2SO4
18. concentrationconcentrated
19. customThe residue was purified by chromatography (on silica gel, ethyl acetate/hexane=15/85)
20. customto yield a colorless oil in 3.8 g

ORD record

ord-26b31df7d6fc4919b0f0d9ef56187d65

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06531494B1