Sodium Carbonate → (2-Cyclopropyl-4'-fluoro-5-isopropoxybiphenyl-4-yl)methanol

A mixture of methyl 2-bromo-4′-fluoro-5-isopropoxybiphenyl-4-carboxylate (7.53 g), cyclopropylboronic acid (4.40 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (1.26 g), a 2 M aqueous sodium carbonate solution (30.8 mL), tris(dibenzylideneacetone)dipalladium(0) (1.31 g), and toluene (150 mL) was stirred overnight at 100° C. in an argon atmosphere. The reaction mixture was allowed to cool to room temperature. Then, the organic layer was separated, washed with saturated saline, and passed through a short silica gel (NH) column, and the solvent was distilled off under reduced pressure. A THF (50 mL) solution of the obtained residue was added to a THF (50 mL) suspension of lithium aluminum hydride (2.00 g) under ice cooling in a nitrogen atmosphere. After stirring at the same temperature as above for 30 minutes, water (2 mL) and a 15% aqueous sodium hydroxide solution (2 mL) were added thereto, and the mixture was stirred for 5 minutes. Water (6 mL) was further added to the reaction mixture, and the mixture was stirred for 30 minutes and then filtered. The filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (5.75 g).

1. customThen, the organic layer was separated
2. washwashed with saturated saline
3. distillationthe solvent was distilled off under reduced pressure
4. additionA THF (50 mL) solution of the obtained residue was added to a THF (50 mL) suspension of lithium aluminum hydride (2.00 g) under ice cooling in a nitrogen atmosphere
5. additiona 15% aqueous sodium hydroxide solution (2 mL) were added
6. stirringthe mixture was stirred for 5 minutes
7. additionWater (6 mL) was further added to the reaction mixture
8. stirringthe mixture was stirred for 30 minutes
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

ORDレコード

ord-d232c9a6f38c4dafbaaa1f3f53c2cf31

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09353108B2