m-Anisoyl chloride → 4-Chloro-2-fluoro-6-(3-methoxybenzoyl)benzonitrile

2-Bromo-4-chloro-6-fluorobenzonitrile (6.95 g, 29.64 mmol) was dissolved in THF (15 mL) and added to a bottle of Rieke® Zinc in THF (50 mg/mL, 50.0 mL, 38.24 mmol) at 0° C. under an argon atmosphere. The resulting mixture was stirred at rt for 6 h and then stored in a refrigerator for 60 h allowing the excess of zinc to settle. The solution was carefully decanted off and cooled to −78° C. under an argon atmosphere. A solution of lithium bromide (5.15 g, 59.28 mmol) and copper(I) cyanide (2.65 g, 29.64 mmol) in THF (30 mL) was added and the resulting mixture was stirred at rt for 30 min. The mixture was cooled to −78° C. and then 3-methoxybenzoyl chloride (4.17 mL, 29.64 mmol) was added dropwise. The cooling bath was removed and the resulting mixture was stirred at rt for 1.5 h. Saturated aqueous NH4Cl (12 mL) was added to the mixture, the THF was removed in vacuo and the residue was diluted with water (50 mL) and DCM (50 mL). The mixture was poured into a phase separator, the organic phase was collected, concentrated and purified on a silica gel column (0-30% EtOAc in heptane) to give 4.7 g (55%) of the title compound.

1. waitstored in a refrigerator for 60 h
2. customThe solution was carefully decanted off
3. temperaturecooled to −78° C. under an argon atmosphere
4. stirringthe resulting mixture was stirred at rt for 30 min
5. temperatureThe mixture was cooled to −78° C.
6. customThe cooling bath was removed
7. stirringthe resulting mixture was stirred at rt for 1.5 h
8. additionSaturated aqueous NH4Cl (12 mL) was added to the mixture
9. customthe THF was removed in vacuo
10. additionthe residue was diluted with water (50 mL) and DCM (50 mL)
11. additionThe mixture was poured into a phase separator
12. customthe organic phase was collected
13. concentrationconcentrated
14. custompurified on a silica gel column (0-30% EtOAc in heptane)

ORDレコード

ord-e6852b5321c84dbb9f7c3449ee6208b3

出典データセット

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08030500B2