Sodium Carbonate → Methyl 2-fluoro-6-(pyrimidin-2-yl)benzoate

HRID 243838Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:20])[C:4]1[C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][CH:7]=[CH:6][C:5]=1[F:19].Cl[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.CC(OC)(C)C>[CH3:1][O:2][C:3](=[O:20])[C:4]1[C:9]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[CH:8][CH:7]=[CH:6][C:5]=1[F:19]

Participants

Conditions

Temperature: 74 °C

Procedure

To a 250 mL round-bottomed flask under nitrogen were added 2-fluoro-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (5.46 g, 19.5 mmol) in 2-methyl-THF (50 mL), 2-chloropyrimidine (2.68 g, 23.4 mmol), and sodium carbonate (6.2 g, 58.5 mmol) in water (17 mL). PdCl2(dppf)-dcm adduct (CAS#72287-26-4) (1.27 g, 1.56 mmol) was then added and the reaction mixture was warmed to 74° C. and stirred for 2.5 h. After cooling, the mixture was diluted with MTBE (50 mL) and water (80 mL). The layers were thoroughly mixed then separated. The aqueous layer was extracted with additional MTBE (100 mL). The combined organics were dried over magnesium sulfate, filtered, concentrated and then purified by flash chromatography (0-25% EA/hexanes) to provide the title compound (1.72 g, 72 wt %, 30% yield). 1H NMR (400 MHz, CDCl3): 8.79 (d, J=4.9 Hz, 2H), 8.15 (d, J=7.9 Hz, 1H), 7.51 (td, J=8.1, 5.6 Hz, 1H), 7.28-7.20 (m, 2H), 3.92 (s, 3H).

Workup

temperatureAfter cooling
additionThe layers were thoroughly mixed
customthen separated
extractionThe aqueous layer was extracted with additional MTBE (100 mL)
dry with materialThe combined organics were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
custompurified by flash chromatography (0-25% EA/hexanes)

Sources & evidence

ORD record: ord-fcb86baaba11463ba28b0efd983d0c30
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653263B2

Reaction notes

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