Lithium diisopropylamide → 7-bromo-2-(diethylamino)-5H-chromeno[2,3-b]pyridin-5-one

HRID 335827Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[N:17]=2)=[C:6]([CH:14]=1)[C:7](N(CC)CC)=[O:8].[CH:23]([N-:26][CH:27](C)[CH3:28])(C)[CH3:24].[Li+]>C1COCC1>[Br:1][C:2]1[CH:14]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:15][C:16]1=[N:17][C:18]([F:22])=[CH:19][CH:20]=[C:21]1[C:7]2=[O:8].[Br:1][C:2]1[CH:14]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:15][C:16]1=[N:17][C:18]([N:26]([CH2:27][CH3:28])[CH2:23][CH3:24])=[CH:19][CH:20]=[C:21]1[C:7]2=[O:8]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 5-bromo-N,N-diethyl-2-(6-fluoropyridin-2-yloxy)benzamide (2.90 g, 7.90 mmol) in 50 mL of dry THF at −78° C. was added dropwise lithium diisopropylamide (2.0 M heptane/THF/ethylbenzene, 11.8 mL, 23.69 mmol) and the reaction was stirred at −78° C. for 2 hours. The reaction quenched at −78° C. with 30 mL of 1 N HCl in ether. After warming to rt, the reaction was further quenched with saturated NH4Cl (250 mL) extracted with ethyl acetate (3×250 mL). The combined organics were washed with brine, and evaporated to dryness. Purification by silica gel chromatography (hexane to hexane/CH2Cl2=1:1 to CH2Cl2 to CH2Cl2/EA=10:1) gave 7-bromo-2-fluoro-5H-chromeno[2,3-b]pyridin-5-one as a white solid and 7-bromo-2-(diethylamino)-5H-chromeno[2,3-b]pyridin-5-one as a white solid.

Workup

customThe reaction quenched at −78° C. with 30 mL of 1 N HCl in ether
temperatureAfter warming to rt
customthe reaction was further quenched with saturated NH4Cl (250 mL)
extractionextracted with ethyl acetate (3×250 mL)
washThe combined organics were washed with brine
customevaporated to dryness
customPurification by silica gel chromatography (hexane to hexane/CH2Cl2=1:1 to CH2Cl2 to CH2Cl2/EA=10:1)

Sources & evidence

ORD record: ord-5951c766dad94fe48de29bfa1efa5157
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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