Sodium Carbonate → 3-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-6-(2,6-difluorobenzyl)-2-(2,4-difluorophenyl)pyridine

HRID 1360705Notes

Reaction equation

[Si:1]([O:8][CH2:9][C:10]1[C:11](Cl)=[N:12][C:13]([CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Si:1]([O:8][CH2:9][C:10]1[C:11]([C:30]2[CH:29]=[CH:28][C:27]([F:26])=[CH:32][C:31]=2[F:33])=[N:12][C:13]([CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 90 °C

Procedure

To a crude 3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-chloro-6-(2,6-difluorobenzyl)pyridine (from Step C above) in DME was added 2,4-difluorophenylboronic acid (6.5 g), tetrakis(triphenylphosphine)palladium (2 g) and 2N Na2CO3 (40 mL), and heated to 90° C. for a couple of hours until reaction completed. The mixture was cooled to room temperature and filtered through celite. The mixture was diluted with ethyl acetate, washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by silica gel (100% methylene chloride) to give title compound (4.81 g).

Workup

temperatureThe mixture was cooled to room temperature
filtrationfiltered through celite
additionThe mixture was diluted with ethyl acetate
washwashed with water, brine
dry with materialdried over MgSO4
concentrationconcentrated
customThe residue was purified by silica gel (100% methylene chloride)

Sources & evidence

ORD record: ord-53ad64c653504dc3936c2afa1d065a91
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879875B2

Reaction notes

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