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

HRID 529391Notes

Reaction equation

HRID 529391 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:15][C:16]2[CH:17]=[N:18][C:19]([Cl:22])=[CH:20][CH:21]=2)=[C:6]([CH:14]=1)[C:7](N(CC)CC)=[O:8].[Li+].CC([N-]C(C)C)C>C1COCC1.CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C>[Br:1][C:2]1[CH:14]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:15][C:16]1[CH:17]=[N:18][C:19]([Cl:22])=[CH:20][C:21]=1[C:7]2=[O:8]

Participants

5

Reactant 2

HCID 2724682Lithium diisopropylamideHCID 574756355-bromo-2-(6-chloropyridin-3-yloxy)-N,N-diethylbenzamide

Product 1

HCID 574756367-Bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-oneYield 9.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 5-bromo-2-(6-chloropyridin-3-yloxy)-N,N-diethylbenzamide (457.5 g, 1.23 mol) in THF (3 L) was cooled to −74 to −78° C. and treated with a solution of LDA (2M in heptane/THF/ethyl benzene, 2.25 L, 4.5 mol. After the addition was complete, the solution was stirred for 30 min at −78° C. The cold bath was removed and then the reaction was quenched with saturated aqueous NH4Cl (1 L), maintaining the temperature below 10° C. The mixture was added to an addition funnel and the layers were separated. The aqueous layer was extracted with EtOAc (3×2.5 L). The combined organic layers were dried over sodium sulfate, filtered and passed through a pad of silica gel. The filtrate was evaporated, and the residue was triturated with DCM to give 35 g of 7-bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-one. The mother liquor was evaporated and the solid thus obtained was purified by recrystallization using dichloromethane/hexanes to give 90 g of 7-bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-one.

Workup

  1. additionAfter the addition
  2. customThe cold bath was removed
  3. customthe reaction was quenched with saturated aqueous NH4Cl (1 L)
  4. temperaturemaintaining the temperature below 10° C
  5. additionThe mixture was added to an addition funnel
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with EtOAc (3×2.5 L)
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. customThe filtrate was evaporated
  11. customthe residue was triturated with DCM

Sources & evidence

ORD record
ord-163bcdf7c0ec4b328ac706c31d390fbc
Source dataset
uspto-grants-2016_05
Patent number
US09346827B2

Reaction notes

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