Sodium Carbonate → 4-(3-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yloxy)aniline

HRID 473681Notes

Reaction equation

Cl[C:2]1[C:3]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[O:16]1[CH2:21][CH:20]=[C:19](B2OC(C)(C)C(C)(C)O2)[CH2:18][CH2:17]1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC.O>C(Cl)Cl.CCOC(C)=O>[O:16]1[CH2:17][CH:18]=[C:19]([C:2]2[C:3]([O:8][C:9]3[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH2:20][CH2:21]1

Participants

Conditions

Temperature: 80 °C

Procedure

Into a sealed tube were placed 4-(3-chloropyrazin-2-yloxy)aniline (1 g, 4.51 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.42 g, 6.77 mmol), dichlorobis(triphenylphosphine) palladium (II) (0.25 g, 0.36 mmol), sodium carbonate (2.39 g, 22.5 mmol) and 18 mL of 4:1 DME-water. After the mixture was degassed for 5 min, the reaction was stirred at 80° C. for 18 h. The cooled reaction was diluted with CH2Cl2 and washed with aqueous saturated NaHCO3 solution; the aqueous layer was back-extracted with CH2Cl2 (1×). The organic extracts were combined, dried (MgSO4), filtered, and concentrated in vacuo. Flash column chromatography (10% to 50% EtOAc (10% MeOH)/Hexanes) afforded 4-(3-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yloxy)aniline (1.09 g, 90% yield) as a light yellow solid. [M+1]=270.1.

Workup

customInto a sealed tube were placed
customAfter the mixture was degassed for 5 min
customThe cooled reaction
washwashed with aqueous saturated NaHCO3 solution
extractionthe aqueous layer was back-extracted with CH2Cl2 (1×)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-27d254ced4d94a2a970ca376939ebb70
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637500B2

Reaction notes

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