Sodium Carbonate → 2-(3,6-dihydro-2H-pyran-4-yl)-3-fluoropyrazine

HRID 2191996Notes

Reaction equation

[F:1][C:2]1[C:7](I)=[N:6][CH:5]=[CH:4][N:3]=1.[O:9]1[CH2:14][CH:13]=[C:12](B2OC(C)(C)C(C)(C)O2)[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[O:9]1[CH2:10][CH:11]=[C:12]([C:7]2[C:2]([F:1])=[N:3][CH:4]=[CH:5][N:6]=2)[CH2:13][CH2:14]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a glass microwave vial was added 2-fluoro-3-iodopyrazine (1.6485 g, 7.36 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.319 g, 11.04 mmol), trans-dichlorobis(triphenylphosphine) palladium (II) (0.413 g, 0.589 mmol), and sodium carbonate (3.90 g, 36.8 mmol) in DME (19.63 mL) and water (4.91 mL) to stir at 80° C. overnight. Reaction was allowed to cool to room temperature. The reaction mixture was diluted with water and extracted with DCM. The organic extract was washed with water, brine, dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (40S), eluting with a gradient of 10% to 100% EtOAc in hexane, to provide 2-(3,6-dihydro-2H-pyran-4-yl)-3-fluoropyrazine. [M+H]=181.1.

Workup

customReaction
temperatureto cool to room temperature
extractionextracted with DCM
extractionThe organic extract
washwas washed with water, brine
dry with materialdried with magnesium sulfate
filtrationfiltered
concentrationconcentrated
customchromatographed through a Biotage pre-packed silica gel column (40S)
washeluting with a gradient of 10% to 100% EtOAc in hexane

Sources & evidence

ORD record: ord-61f0047d40484244a719b9b351bbc4b9
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329700B2

Reaction notes

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