4-(Bromomethyl)-1,2-difluorobenzene → 2-(3,4-Difluorobenzyloxy)-6-(2-chlorophenyl)-5-(4-chlorophenyl)nicotinonitrile

HRID 916978Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:13][C:12](=[O:14])[C:11]([C:15]#[N:16])=[CH:10][C:9]=1[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1.[F:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][C:32]=1[F:33])[CH2:28]Br>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)=[CH:10][C:11]([C:15]#[N:16])=[C:12]([O:14][CH2:28][C:27]2[CH:30]=[CH:31][C:32]([F:33])=[C:25]([F:24])[CH:26]=2)[N:13]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To the product of Step C (0.500 g, 1.465 mmol) was added Ag2CO3 (0.606 g, 2.198 mmol), DMF (8 mL), and 3,4-difluorobenzyl bromide (0.28 mL, 2.198 mmol). The reaction was heated to 75° C. for 75 min before cooling and filtering through Celite®545 diatomaceous earth. The solution was concentrated and the residue was purified by flash chromatography (silica gel) eluting with a gradient of 15 to 46% ethyl acetate/hexane affording the product. MS (electrospray) m/e 467.0 MH+ (Rt=4.7 min LC/MS).

Workup

temperaturebefore cooling
filtrationfiltering through Celite®545 diatomaceous earth
concentrationThe solution was concentrated
customthe residue was purified by flash chromatography (silica gel)
washeluting with a gradient of 15 to 46% ethyl acetate/hexane affording the product

Sources & evidence

ORD record: ord-f3c3415d2d964ea8897ff7f104465992
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07271266B2

Reaction notes

Loading…