Potassium Acetate → (6-((1,3-Dioxoisoindolin-2-yl)methyl)pyridin-3-yl)boronic acid

HRID 877778Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])=[N:6][CH:7]=1.CC1(C)C(C)(C)[O:24][B:23](B2OC(C)(C)C(C)(C)O2)[O:22]1.C([O-])(=O)C.[K+]>O1CCOCC1>[O:19]=[C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:17](=[O:18])[N:9]1[CH2:8][C:5]1[N:6]=[CH:7][C:2]([B:23]([OH:24])[OH:22])=[CH:3][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a mixture of 2-((5-bromopyridin-2-yl)methyl)isoindoline-1,3-dione (317 mg, 1.000 mmol) and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (381 mg, 1.499 mmol) in dioxane (10 mL) at rt under nitrogen was added potassium acetate (294 mg, 3.00 mmol), followed by PdCl2(dppf)-CH2Cl2Adduct (82 mg, 0.100 mmol). At this time, the reaction mixture was heated to 70° C. under nitrogen for 5 hr. After cooling to rt, the solvent was removed on the rotovap and the residue was taken up in EtOAc (30 ml). The mixture was filtered through celite and the filter cake was thoroughly washed with EtOAc. The EtOAc filtrate was concentrated to afford (6-((1,3-dioxoisoindolin-2-yl)methyl)pyridin-3-yl)boronic acid (280 mg, 0.993 mmol, 99% yield) as a brown oil. This material was used as is in the next step. MS (ES+) m/z: 283.1 (M+H); LC retention time: 0.54 min (analytical LCMS Method B).

Workup

temperatureAfter cooling to rt
customthe solvent was removed on the rotovap
filtrationThe mixture was filtered through celite
washthe filter cake was thoroughly washed with EtOAc
concentrationThe EtOAc filtrate was concentrated

Sources & evidence

ORD record: ord-9edec2512804429588148e30d01b3d92
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987268B2

Reaction notes

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