Sodium hydride → HCID 18723402, compound

To a dried flask charged with tert-butyl 4-hydroxypiperidine-1-carboxylate (3.60 g, 17887 μmol) was added dry DMF (40 mL) and the resulting solution cooled in an ice water bath prior to the addition of NaH (60% in mineral oil) (748 mg, 18781 μmol) in two portions 5 min apart. The reaction mixture was stirred for 1 hr and allowed to warm to RT over that time. The resulting suspension was cooled in an ice water bath prior to the addition of a solution of 1-(bromomethyl)-4-(trifluoromethoxy)benzene (5018 mg, 19676 μmol) in DMF (5 mL) via syringe. The resulting reaction mixture was allowed to slowly warm to RT while stirring for 15 h. The resulting pale yellow suspension was carefully diluted with water (about 150 mL) and extracted 2× with EtOAc. The combined organics were dried with Na2SO4, filtered and concentrated under reduced pressure. The material was purified through silica gel column chromatography ramping ethyl acetate in hexanes from 0% to 10% over 5 mins, then remaining at 10% for 10 min, then ramping to 50% over 5 min providing tert-butyl 4-(4-(trifluoromethoxy)benzyloxy)-piperidine-1-carboxylate (5 g) as a white crystalline solid upon drying.

1. temperaturethe resulting solution cooled in an ice water bath
2. temperatureThe resulting suspension was cooled in an ice water bath
3. customThe resulting reaction mixture
4. temperatureto slowly warm to RT
5. stirringwhile stirring for 15 h
6. extractionextracted 2× with EtOAc
7. dry with materialThe combined organics were dried with Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe material was purified through silica gel column chromatography
11. customover 5 mins
12. waitremaining at 10% for 10 min
13. waitramping to 50% over 5 min

ORD record

ord-67d98cf9b4814ed8b20910a69c3391ac

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09334269B2