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

HRID 1193100Notes

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 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
customseparated
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-e6aa7b59d5bf4431a294379bfcaa1ac1
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680275B2

Reaction notes

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