Toluene → 1-(t-Butoxycarbonyl)-4-(3,3-difluoro-3-(2-pyridyl)prop-1-en-1-yl)piperidine

A suspension of ((1-(t-butoxycarbonyl)piperidin-4-yl)methyl)triphenylphosphonium iodide (5.29 g, 9.00 mmol, from Procedure 17, Step C) in THF (70 mL) was stirred at rt for 40 min. A toluene solution of potassium bis(trimethylsilyl)amide (18 mL, 0.5 M, 9.0 mmol) was added, giving an orange suspension. After 40 min., crude 2,2-difluoro-2-(2-pyridyl)-1-methoxyethanol (940 mg, 4.97 mmol) was added in THF (20 mL). After an additional 50 min., the mixture was quenched by the addition of saturated aq. NH4Cl (10 mL). The mixture was partitioned between ethyl acetate (100 mL) and water (100 mL), and the aqueous layer was extracted with ethyl acetate (3×100 mL). The organic layers were washed in succession with saturated aq. brine (100 mL), dried (sodium sulfate), decanted, and evaporated. Purification by flash column chromatography on silica gel, eluting with 90:10 v/v to 80:20 v/v hexanes/ethyl acetate, gave 1.18 mg of the title compound (approximately 95:5 cis/trans mixture) as an oil which solidified upon standing. For the title compound:

1. customgiving an orange suspension
2. waitAfter 40 min.
3. waitAfter an additional 50 min.
4. customthe mixture was quenched by the addition of saturated aq. NH4Cl (10 mL)
5. customThe mixture was partitioned between ethyl acetate (100 mL) and water (100 mL)
6. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
7. washThe organic layers were washed in succession with saturated aq. brine (100 mL)
8. dry with materialdried (sodium sulfate)
9. customdecanted
10. customevaporated
11. customPurification by flash column chromatography on silica gel
12. washeluting with 90:10 v/v to 80:20 v/v hexanes/ethyl acetate

ORD-Eintrag

ord-c29cc7a64a5b4949a338a3e8fc3c11b5

Quelldatensatz

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06432981B1