Lithium diisopropylamide → 7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-one

HRID 1855295Notes

Reaction equation

HRID 1855295 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:15][C:16]2[C:17]([F:23])=[N:18][C:19]([Cl:22])=[CH:20][CH:21]=2)=[C:6]([CH:14]=1)[C:7](N(CC)CC)=[O:8].C([N-]C(C)C)(C)C.[Li+].CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C>C1COCC1>[Br:1][C:2]1[CH:14]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:15][C:16]1[C:17]([F:23])=[N:18][C:19]([Cl:22])=[CH:20][C:21]=1[C:7]2=[O:8]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzolHCID 86640732HCID 86640732, compound

Product 1

HCID 574756427-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-bromo-2-(6-chloro-2-fluoropyridin-3-yloxy)-N,N-diethylbenzamide (120 mg, 0.299 mmol) in 5 mL of dry THF at −78° C. was added dropwise lithium diisopropylamide, 2.0M heptane/THF/ethylbenzene (158 μL, 1.195 mmol) (0.6 mL of 2M solution) and the reaction was stirred at −78° C. for 3 h. The reaction was quenched at −78° C. with sat. NH4Cl and was allowed to warm up to RT. The reaction was extracted with ETOAc, dried over Na2SO4, filtered and evaporated to dryness. The crude was purified by column chromatography (1:1 hexane/DCM to 100% DCM) to give the titled compound, 7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-one, as an offwhite solid. MS (M+1): 328.

Workup

  1. customThe reaction was quenched at −78° C. with sat. NH4Cl
  2. temperatureto warm up to RT
  3. extractionThe reaction was extracted with ETOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe crude was purified by column chromatography (1:1 hexane/DCM to 100% DCM)

Sources & evidence

ORD record
ord-292ef61033a547029fd7f788d58d8c3a
Source dataset
uspto-grants-2015_02
Patent number
US08962859B2

Reaction notes

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