Cesium carbonate → HCID 63962346, compound

HRID 1855100Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13](Br)[N:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].[OH-].[Na+]>CN1CCCC1=O.CCOC(C)=O>[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:9][C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=2)[N:12]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3,4-difluorophenol (1.55 g, 11.9 mmol), 2,6-dibromopyridine (2.82 g, 11.9 mmol), and Cs2CO3 (3.88 g, 11.9 mmol) in N-Methyl-2-pyrrolidinone (10 mL) was stirred at 100° C. for 18 h, then was cooled to rt. EtOAc (10 mL) and 1N aq. NaOH (20 mL) were added to the reaction mixture. The organic layer was separated and washed with water (3×) and brine, dried (MgSO4), and filtered. The filtrate was concentrated in vacuo. The crude product was chromatographed (SiO2; continuous gradient of EtOAc/hexanes from 0% to 10% over 12 min) to give the title compound (2.90 g, 10.1 mmol, 85% yield) as a clear oil, which eventually became a white solid. 1H NMR (CDCl3) δ: 7.56 (t, J=7.8 Hz, 1H), 7.24 (d, J=7.5 Hz, 1H), 7.18 (q, J=9.1 Hz, 1H), 7.06-7.00 (m, 1H), 6.92-6.87 (m, 1H), 6.85 (d, J=8.1 Hz, 1H); 19F NMR (CDCl3) δ: −134.55 (d, J=21.4 Hz), −142.14 (d, J=21.3 Hz).

Workup

temperaturewas cooled to rt
customThe organic layer was separated
washwashed with water (3×) and brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo
customThe crude product was chromatographed (SiO2; continuous gradient of EtOAc/hexanes from 0% to 10% over 12 min)

Sources & evidence

ORD record: ord-a40d15efb90341cd99836a244ff47c34
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962660B2

Reaction notes

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