Boron trifluoride etherate → 2-(5-azido-7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-yl)ethanol

HRID 931578Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:15](=[CH:16][CH:17]=1)[O:14][C:7]1[C:8]([F:13])=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C:5]2([CH2:19][CH2:20][OH:21])O.[N:22]([Si](C)(C)C)=[N+:23]=[N-:24].B(F)(F)F.CCOCC>C1COCC1>[N:22]([C:5]1([CH2:19][CH2:20][OH:21])[C:6]2[CH:11]=[C:10]([Cl:12])[N:9]=[C:8]([F:13])[C:7]=2[O:14][C:15]2[C:4]1=[CH:3][C:2]([Br:1])=[CH:17][CH:16]=2)=[N+:23]=[N-:24]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 7-bromo-3-chloro-1-fluoro-5-(2-hydroxyethyl)-5H-chromeno[2,3-c]pyridin-5-ol (48 g, 128 mmol) in THF (58 mL) were added azidotrimethylsilane (34.0 ml, 256 mmol) and boron trifluoride diethyl etherate (31.6 ml, 256 mmol). The reaction mixture was heated to 60° C. for 15 h. Additional azidotrimethylsilane (34.0 ml, 256 mmol) and boron trifluoride diethyl etherate (31.6 ml, 256 mmol) were added and heating was continued for 3 h. The reaction mixture was quenched with aqueous, saturated NaHCO3 solution and extracted with EtOAc. The organic phase was separated, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography (0-30% EtOAc/hexanes) to afford 2-(5-azido-7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-yl)ethanol (41 g, 103 mmol, 80% yield) as a pale yellow solid-foam.

Workup

temperatureheating
customThe reaction mixture was quenched with aqueous, saturated NaHCO3 solution
extractionextracted with EtOAc
customThe organic phase was separated
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customThe residue was purified by chromatography (0-30% EtOAc/hexanes)

Sources & evidence

ORD record: ord-6ba8a8c216a7441f9ab5b38c33b76a69
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296759B2

Reaction notes

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