Tetrahydrofuran → 4-Bromo-1-fluoronaphthalene-2-carbaldehyde

A solution of 2,2,6,6-tetramethylpiperidine (4.13 ml) in tetrahydrofuran (40 ml) was cooled to −78° C. under argon atmosphere, and added dropwise thereto was n-butyl lithium (2.44 M hexane solution, 10.0 ml). The mixture was stirred at the same temperature for 30 minutes, and added dropwise thereto at −78° C. was a solution of 1-bromo-4-fluoronaphthalene (5.0 g) in tetrahydrofuran (20 ml). The mixture was stirred at the same temperature for 1 hour, and added dropwise thereto at −78° C. was N,N-dimethylformamide (5.16 ml). The mixture was stirred at the same temperature for 1 hour, and added thereto was a saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was crystallized from diisopropyl ether and hexane to give 4-bromo-1-fluoro-2-naphthaldehyde (4.43 g) as pale yellow crystals. APCI-Mass m/Z 267/269 (M+NH4). (2) The above 4-bromo-1-fluoro-2-naphthaldehyde and 2-(2-pyridyl)thiophene were treated in a manner similar to Reference Example 120 to give the desired 4-bromo-1-fluoro-2-(5-(2-pyridyl)-2-thienylmethyl)naphthalene as colorless powder. APCI-Mass m/Z 398/400 (M+H).

1. additionadded dropwise
2. additionadded dropwise
3. customat −78° C.
4. stirringThe mixture was stirred at the same temperature for 1 hour
5. additionadded dropwise
6. customat −78° C.
7. stirringThe mixture was stirred at the same temperature for 1 hour
8. additionadded
9. extractionthe mixture was extracted with ethyl acetate
10. washThe extract was washed with water
11. dry with materialdried over magnesium sulfate
12. customthe solvent was evaporated under reduced pressure
13. customThe residue was crystallized from diisopropyl ether and hexane

ORD record

ord-e3c983b9291d43a1af0e35108f38678e

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08222219B2