Benzoic Acid → (trans)-Benzyl 4-(benzoyloxy)-3-fluoropiperidine-1-carboxylate

Temperature

0 °C

Non-racemic (cis)-benzyl 3-fluoro-4-hydroxypiperidine-1-carboxylate (Peak 1 of Example 94, Step 3D; 0.306 g, 1.21 mmol) was treated with triphenylphosphine (0.475 g, 1.81 mmol) and benzoic acid (0.221 g, 1.81 mmol) and the solids were dissolved in THF (5 mL), then cooled to 0° C. The solution was treated dropwise with diisopropyl azodicarboxylate (0.357 mL, 1.81 mmol) dissolved in THF (1 mL). The solution was warmed to ambient temperature with a bath and stirred for 7 days, then concentrated in vacuo. The residue was dissolved in CH2Cl2 and washed with saturated NH4Cl, water, 50% saturated NaHCO3, dried over Na2SO4 and concentrated in vacuo to a colorless oil. The oil was chromatographed on SiO2 eluting with 1:12 acetone/hexanes. The desired fraction was isolated to provide the desired product as a colorless oil (385 mg).

1. temperatureThe solution was warmed to ambient temperature with a bath
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in CH2Cl2
4. washwashed with saturated NH4Cl, water, 50% saturated NaHCO3
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in vacuo to a colorless oil
7. customThe oil was chromatographed on SiO2 eluting with 1:12 acetone/hexanes
8. customThe desired fraction was isolated

ORD record

ord-bdb257b987a6429ab436a52ea7295681

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575145B2