Tributylphosphine → 4-(4-Chlorophenyl)-3-(3-cyanophenyl)-2-butanol

Temperature

115 °C

To a solution of 4-(4-chlorophenyl)-3-(3-bromophenyl)-2-butanol (1.5 kg, 4.6 mol) in dimethylformamide/water (volume ratio 99:1, 15 L total) was added zinc cyanide (0.39 kg, 3.3 mol), 1,1′-bis(diphenylphosphino)ferrocene (115 g, 0.21 mol) and tris(dibenzylideneacetone)dipalladium (76 g, 0.08 mol). The reaction mixture was stirred and degassed at room temperature for 1 h, and heated at 115° C. for 6 h before cooling to room temperature. Tributylphosphine (46 mL, 0.17 mol) was then added. After stirring for 1 h, the reaction was quenched with aqueous ammonia (1.56 L). After stirring for 1 h, the mixture was filtered through solka floc, and the cake was washed with isopropyl acetate. The filtrate was washed with water (5 L), and the aqueous layer was extracted with isopropyl acetate (4 L). The organic layers were combined, washed with water (10 L×2) and concentrated to give the title compound, which was used for the ensuing reaction after azeotroping with toluene.

1. customdegassed at room temperature for 1 h
2. temperaturebefore cooling to room temperature
3. stirringAfter stirring for 1 h
4. customthe reaction was quenched with aqueous ammonia (1.56 L)
5. stirringAfter stirring for 1 h
6. filtrationthe mixture was filtered through solka floc
7. washthe cake was washed with isopropyl acetate
8. washThe filtrate was washed with water (5 L)
9. extractionthe aqueous layer was extracted with isopropyl acetate (4 L)
10. washwashed with water (10 L×2)
11. concentrationconcentrated

ORD record

ord-e70693eb204d462a94aa2a37fe51724e

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07754188B2