N,N,N',N'-Tetramethylethylenediamine → HCID 68970431, compound

Temperature

-78 °C

To a −78° C. solution of 1-bromo-4-trifluoromethylbenzene (32.9 g, 146 mmol) in anhydrous THF (500 mL) was added n-BuLi (2.5M in Hexanes, 63.4 mL, 158 mmol) dropwise. The mixture was stirred at −78° C. for 1 hour. TMEDA (22.1 mL, 146 mmol) was added followed by 4-formyl-piperidine-1-carboxylic acid tert-butyl ester (26.0 g, 122 mmol) and the mixture was stirred at −78° C. for 1.5 hours. Saturated aqueous NH4Cl (5000 mL) was added and the mixture was warmed to room temperature. The phases were separated and the aqueous phase was extracted with EtOAc (2×300 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The crude material was crystallized (CH2Cl2/Hexanes) to give 4-[hydroxy-(4-trifluoromethylphenyl)-methyl]-piperidine-1-carboxylic acid tert-butyl ester as a white solid (29.0 g). The mother liquor was purified by column chromatography to give further product (3.8 g) as a white solid (combined yield: 32.8 g, 75%). 1H NMR (CDCl3) δ 1.15-1.32 (m, 3H), 1.44 (s, 9H), 1.68-1.81 (m, 1H), 1.89 (d, 1H, J=13.8 Hz), 1.98 (br s, 1H), 2.54-2.68 (m, 2H), 4.12 (br s, 2H), 7.43 (d, 2H, J=8.7 Hz), 7.62 (d, 2H, J=8.7 Hz).

1. stirringthe mixture was stirred at −78° C. for 1.5 hours
2. temperaturethe mixture was warmed to room temperature
3. customThe phases were separated
4. extractionthe aqueous phase was extracted with EtOAc (2×300 mL)
5. dry with materialThe combined organic extracts were dried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude material was crystallized (CH2Cl2/Hexanes)

ORD record

ord-7a860b3108cb4763b80c5d63ffc92a6f

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07491735B2