tert-Butyl 4-oxopiperidine-1-carboxylate → 4-Hydroxy-4-(3-methylsulfanylphenyl)-piperidin-1-carboxylic acid tert-butyl ester

Temperature

-78 °C

1-Bromo-3-methylsulfanyl-benzene (5.0 g, 24.6 mmol) was dissolved in dry THF (40 ml) and cooled to −78° C. under a stream of Argon (g). n-BuLi (12.8 ml, 2.5 M in hexane, 31.9 mmol) was added dropwise via syringe and the reaction mixture was stirred for an additional 30 min at −78° C., then the temperature was increased to 0° C. for 5 min and then decreased to −78° C. 1-tert-Butoxycarbonyl-4-piperidone (5.4 g, 27.06 mmol) dissolved in dry THF (30 ml) was added via syringe. The reaction mixture was allowed to reach room temperature and then stirred for 1 hour, and finally quenched with saturated ammonium chloride solution (30 ml). The mixture was extracted several times with EtOAc and the combined organic phases were dried (MgSO4), filtered and evaporated to dryness. The oily residue was chromatho-graphed on a silica column using CH2Cl2:MeOH (19:1 (v/v)) as eluent, yielded 4-hydroxy-4-(3-methylsulfanyl-phenyl)-piperidin-1-carboxylic acid tert-butyl ester (6 g, 76%). MS m/z (relative intensity, 70-eV) 323.1 (M+, 6), 223.0 (11), 178.0 (7), 152 (3), 57.0 (bp), 56 (30).

1. temperaturethe temperature was increased to 0° C. for 5 min
2. customdecreased to −78° C
3. additionwas added via syringe
4. customto reach room temperature
5. stirringstirred for 1 hour
6. customfinally quenched with saturated ammonium chloride solution (30 ml)
7. extractionThe mixture was extracted several times with EtOAc
8. dry with materialthe combined organic phases were dried (MgSO4)
9. filtrationfiltered
10. customevaporated to dryness

ORD record

ord-9cda1f7f560f4ae2a195eb5b7147a7a3

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07417043B2