Dichloromethane → HCID 117858280, compound

HRID 1486325Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:24](B(O)O)[CH3:25].ClCCl>O1CCOCC1.O>[F:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([F:16])[C:10]=1[CH2:9][O:8][C:4]1[CH:3]=[C:2]([CH2:24][CH3:25])[CH:7]=[CH:6][N:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 3.8 g (9.24 mmol, 73% purity) of 4-bromo-2-[(2,6-difluorobenzyl)oxy]pyridine (Example 145A) in 54 ml of 1,4-dioxane and 13 ml of water was degassed under argon for 10 minutes. The solution was admixed with 9.04 g (27.73 mmol) of caesium carbonate, 0.82 g (11.09 mmol) of ethylboronic acid (CAS: 4433-63-0) and 0.75 g (0.924 mmol) of (1,1)-bis(diphenylphosphino)ferrocenedichloropalladium(II) complex with dichloromethane (CAS: 95464-05-4). The reaction vessel was closed and the contents were stirred at 100° C. for 18 hours. The solvent was evaporated off and the residue was partitioned between water and ethyl acetate. The organic phase was removed and concentrated under reduced pressure. The residue was purified by flash chromatography using a prepacked silica gel cartridge (eluent:cyclohexane/ethyl acetate, gradient 0% to 5%), which gave 1.38 g (41% yield, 69% purity) of product.

Workup

customThe reaction vessel was closed
customThe solvent was evaporated off
customthe residue was partitioned between water and ethyl acetate
customThe organic phase was removed
concentrationconcentrated under reduced pressure
customThe residue was purified by flash chromatography
customgave 1.38 g (41% yield, 69% purity) of product

Sources & evidence

ORD record: ord-88fa7f3380d24c42a599a5ca48f6c547
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422285B2

Reaction notes

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