1,2-Dimethoxyethane → 5'-Chloro-2'-fluoro-6-(3-fluorobenzyloxy)-2,4'-bipyridine

HRID 1963869Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)[N:3]=1.[Cl:17][C:18]1[C:19](B(O)O)=[CH:20][C:21]([F:24])=[N:22][CH:23]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.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>[Cl:17][C:18]1[C:19]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=3)[N:3]=2)=[CH:20][C:21]([F:24])=[N:22][CH:23]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-bromo-6-(3-fluorobenzyloxy)pyridine (145 mg, 0.514 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (144 mg, 0.822 mmol), PalladiumTetrakis (71.3 mg, 0.062 mmol), DME (3 ml), and 12M sodium carbonate (1.028 ml, 2.056 mmol) was reaction mixture was stirred at 100° C. for 3 hr, followed by LCMS. The reaction mixture was cooled, diluted with 10 ml of ethyl acetate, filtered and concentrated to yield a crude product, which was purified by silica gel chromatography using a 12 g column eluting from 0%-20% ethyl acetate with hexane. The desired fractions were concentrated to constant mass, giving 100 mg of titled compound as a free base. LCMS (m/z): 333.1 (MH+), retention time=1.26 min.

Workup

customreaction mixture
temperatureThe reaction mixture was cooled
filtrationfiltered
concentrationconcentrated
customto yield a crude product, which
customwas purified by silica gel chromatography
washeluting from 0%-20% ethyl acetate with hexane
concentrationThe desired fractions were concentrated to constant mass

Sources & evidence

ORD record: ord-d5698488a57246b6ba5c7c7a28c04498
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415381B2

Reaction notes

Loading…