4-Nitrobenzoic Acid → HCID 86681863, compound

To a THF (909 ml) solution of benzyl (2R,5S)-5-hydroxy-2-methylpiperidine-1-carboxylate (34 g, 136 mmol), 4-(dimethylamino) phenyldiphenylphosphine (58.3 g, 191 mmol), and 4-nitrobenzoic acid (29.6 g, 177 mmol) was added, under N2, DEAD (30.0 ml, 191 mmol) dropwise at −15 to −25° C. over 20 min. The reaction was allowed to warm to RT overnight. The reaction was concentrated in vacuo, removing most THF, then diluted with Et2O (500 mL). The mixture was cooled at 0° C. and washed with 1 N HCl (5×200 mL). The combined aqueous phases were back-extracted twice with Et2O. The combined organic phases were subsequently washed twice more with 1 N HCl. The organics were dried over MgSO4, filtered, and concentrated. The crude material was purified by silica gel gradient chromatography (0-40% ethyl acetate in hexanes), providing the titled compound as a light yellow oil which slowly solidified. LRMS m/z (M+H) 399.3 found, 399.1 required.

1. concentrationThe reaction was concentrated in vacuo
2. customremoving most THF
3. additiondiluted with Et2O (500 mL)
4. temperatureThe mixture was cooled at 0° C.
5. washwashed with 1 N HCl (5×200 mL)
6. extractionThe combined aqueous phases were back-extracted twice with Et2O
7. washThe combined organic phases were subsequently washed twice more with 1 N HCl
8. dry with materialThe organics were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude material was purified by silica gel gradient chromatography (0-40% ethyl acetate in hexanes)

ORD record

ord-b20b2f083f0b4dfcbb66355c481533f7

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156819B2