Toluene → 1-(t-Butoxycarbonyl)-4-(3,3-difluoro-3-(4-fluorophenyl)prop-1-en-1-yl)piperidine

A suspension of ((1-(t-butoxycarbonyl)piperidin-4-yl)methyl)triphenylphosphonium iodide (500 mg, 0,92 mmol) from Step C in THF (7.2 mL) was stirred at rt for 30 min. A 0.5 M toluene solution of potassium bis(trimethylsilyl)amide (1.8 mL, 0.90 mmol) was added over 3 min., giving an orange suspension. After 30 min., crude 2,2-difluoro-2-(4-fluorophenyl)-1-methoxyethanol (95 mg, 0.46 mmol) was added in THF (1.0 mL). After an additional 30 min, the mixture was quenched by the addition of saturated aq. NH4Cl (2 mL). The mixture was partitioned between ethyl acetate (50 mL) and water (75 mL), and the aqueous layer was extracted with ethyl acetate (50 mL). The organic layers were washed in succession with saturated aq. brine (25 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 10% ether in hexane to give 117 mg of the title compound as a 95:5 mixture of cis and trans isomers, respectively.

1. customgiving an orange suspension
2. waitAfter 30 min.
3. waitAfter an additional 30 min
4. customthe mixture was quenched by the addition of saturated aq. NH4Cl (2 mL)
5. customThe mixture was partitioned between ethyl acetate (50 mL) and water (75 mL)
6. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
7. washThe organic layers were washed in succession with saturated aq. brine (25 mL)
8. dry with materialdried (sodium sulfate)
9. customdecanted
10. customevaporated
11. customThe crude product was purified by FC
12. washeluting with 10% ether in hexane

ORD record

ord-a49074f86c484d29a6f836989b2a2977

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06358979B1