Diisopropylamine → 5-(2,4-Difluorophenyl)pyridine-3-carboxylic acid

HRID 1909144Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1B(O)O.[Na+].[Na+].[Na+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1.C(NC(C)C)(C)C>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-bromonicotinic acid (0.5 g, 2.48 mmol) in DMF (7.4 mL) and water (2.5 mL) were added (2,4-difluorophenyl)boronic acid (0.43 g, 2.72 mmol), palladium acetate (27.8 mg, 0.12 mmol), 3,3′,3″-phosphinidynetris (benzensulfonic acid) trisodium salt (0.21 g, 0.37 mmol) and diisopropylamine (1.23 mL, 8.66 mmol). The mixture was heated to 80° C. After 1.5 h, the mixture was cooled to ambient temperature and filtered. The filtrate was purified by reverse chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid). The product was converted to hydrochloride salt by adding HCl (2.0 M in ether) and concentrated to give the hydrochloride salt of the title compound (0.65 g). MS 236.0 (M+1).

Workup

temperaturethe mixture was cooled to ambient temperature
filtrationfiltered
customThe filtrate was purified by reverse chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)
additionby adding HCl (2.0 M in ether)
concentrationconcentrated

Sources & evidence

ORD record: ord-7f45f25ad0b64656b9e7951b3498a3f9
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598209B2

Reaction notes

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