Pyridine → benzyl 4-(2,3-dichlorophenyl)pyridine-1(4H)-carboxylate

Temperature

0 °C

To a −30° C. solution of 1-bromo-2,3-dichlorobenzene (10 g, 44 mmol) in THF (120 mL) was added i-PrMgCl (2.0 M in THF, 35 mL, 70 mmol) at a rate such that the temperature <−20° C. Meanwhile, to a −10° C. solution of CuI (420 mg, 2.2 mmol) in THF (120 mL) was added pyridine (7.1 mL, 88 mmol) and then benzyl carbonochloridate (9.7 mL, 68 mmol) such that the temperature <0° C. To this heterogeneous mixture was added the initially formed Grignard at a rate such that the temperature <0° C. The resulting solution was stirred at 0° C. for 30 min and then allowed to warm to rt. The reaction was then quenched with 10% aq NH4Cl. EtOAc was added and the blue aq layer was removed. The organic layer was washed with 10% aq NH4Cl, 1 N HCl, and a 20% aq NaCl solution. The organic layer was then concentrated and the residue was dissolved and crystallized from MeOH. The slurry was filtered and the filtercake washed with MeOH to give benzyl 4-(2,3-dichlorophenyl)pyridine-1(4H)-carboxylate (intermediate 45) (12 g, 76%) as an off-white solid. HPLC: 99%, RT 4.118 min. MS (ESI) m/z 382.0 [M+Na]+. mp: 69-70° C.

1. customthat the temperature <0° C
2. additionTo this heterogeneous mixture was added the initially formed Grignard at a rate such that the temperature <0° C
3. temperatureto warm to rt
4. customThe reaction was then quenched with 10% aq NH4Cl
5. additionEtOAc was added
6. customthe blue aq layer was removed
7. washThe organic layer was washed with 10% aq NH4Cl, 1 N HCl
8. concentrationThe organic layer was then concentrated
9. dissolutionthe residue was dissolved
10. customcrystallized from MeOH
11. filtrationThe slurry was filtered
12. washthe filtercake washed with MeOH

ORD record

ord-187fad29b6c84fcbb850b5a160482a05

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156822B2