1-Bromo-3-methylbutane → 4-Methyl-1-{6-[4-(trifluoromethyl)phenyl]-2-pyridinyl}-1-pentanol

Temperature

0 °C

A solution of 6-[4-(trifluoromethyl)phenyl]-2-pyridinecarbaldehyde (350 mg, 1.39 mmol) in Et2O (14 mL) was cooled to 0° C. To this was slowly added the freshly prepared Grignard reagent (1.26 mL, 1.53 mmol), prepared from magnesium turnings (500 mg, 0.02 mol) and 1-bromo-3-methyl butane (2.34 mL, 0.02 mol) in dry Et2O (16.5 mL). The resulting mixture was stirred under nitrogen at 0° C. After 1.5 hours, more Grignard reagent (0.3 mL, 0.36 mmol) was added and the resulting mixture stirred at 0° C. for a further 1.5 hours. The reaction mixture was then quenched by cautious addition of aqueous HCl (2M, 3 mL) and the solvent removed under vacuum. The residue was partitioned between EtOAc (30 mL) and water (20 mL), the layers separated and the aqueous re-extracted with EtOAc (30 mL). The combined organic layer was washed with brine (50 mL), dried (MgSO4) and reduced under vacuum. Purification by SPE (silica, 20 g cartridge), eluting with cyclohexane:EtOAc (gradient 99:1 to 1:1) followed by EtOAc then MeOH afforded the title compound as a colourless oil (179 mg).

1. stirringthe resulting mixture stirred at 0° C. for a further 1.5 hours
2. customThe reaction mixture was then quenched by cautious addition of aqueous HCl (2M, 3 mL)
3. customthe solvent removed under vacuum
4. customThe residue was partitioned between EtOAc (30 mL) and water (20 mL)
5. customthe layers separated
6. extractionthe aqueous re-extracted with EtOAc (30 mL)
7. washThe combined organic layer was washed with brine (50 mL)
8. dry with materialdried (MgSO4)
9. customPurification by SPE (silica, 20 g cartridge)
10. washeluting with cyclohexane

ORD record

ord-1a7555c701394f838107def8c7d5b1e8

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07338960B2