Pyridazine → 7-Phenyl-1-(pyridazin-3-yl)-heptan-1-ol

Temperature

0 °C

2,2,6,6-Tetramethylpiperidine (1.54 mL) was dissolved in anhydrous THF (60 mL) and treated dropwise with 2.0 M n-BuLi (4 equiv) at −40° C. The reaction mixture was stirred at 0° C. for 0.5 h, cooled to −78° C. and treated with a solution of pyridazine (165 μL, 2.26 mmol) in THF (4 mL) immediately followed by a solution of 7-phenylheptanal (435 mg, 2.29 mmol) in THF (2 mL). The reaction mixture was stirred at −78° C. for 1 h before being quenched by the addition of 1 N HCl/EtOH/THF (2/9/9, 40 mL). The reaction mixture was diluted with EtOAc, and washed with H2O, saturated aqueous NaHCO3 and saturated aqueous NaCl. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. Flash chromatography (SiO2, 3×15 cm, 1% MeOH—CH2Cl2) afforded the alcohol (135 mg, 22%) as colorless oil: 1H NMR (CDCl3, 500 MHz) δ 9.12 (dd, 1H, J=1.8, 4.7 Hz), 7.49 (m, 2H), 7.26 (m, 2H), 7.17 (m, 3H), 4.97 (td, 1H, J=4.9, 8.0 Hz), 3.60 (d, 1H(—OH), J=5.4 Hz), 2.58 (t, 2H, J=7.7 Hz), 1.88 (m, 1H), 1.77 (m, 1H), 1.43 (m, 2H), 1.34 (m, 6H).

1. temperaturecooled to −78° C.
2. stirringThe reaction mixture was stirred at −78° C. for 1 h
3. custombefore being quenched by the addition of 1 N HCl/EtOH/THF (2/9/9, 40 mL)
4. additionThe reaction mixture was diluted with EtOAc
5. washwashed with H2O, saturated aqueous NaHCO3 and saturated aqueous NaCl
6. dry with materialThe organic layer was dried over Na2SO4
7. customthe solvent was removed under reduced pressure

ORD record

ord-925355cbce78437d954da0f8781ce8f7

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987312B2