Diethyl Ether → ethyl 2-(7-bromo-3-chloro-5-hydroxy-5H-chromeno[2,3-c]pyridin-5-yl)acetate

HRID 455595Notes

Reaction equation

HRID 455595 reaction equation
C(OCC)C.BrBr.Br[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].[Br:15][C:16]1[CH:17]=[C:18]2[C:28](=[CH:29][CH:30]=1)[O:27][C:21]1[CH:22]=[N:23][C:24]([Cl:26])=[CH:25][C:20]=1[C:19]2=[O:31]>[Zn].C1COCC1>[Br:15][C:16]1[CH:17]=[C:18]2[C:28](=[CH:29][CH:30]=1)[O:27][C:21]1[CH:22]=[N:23][C:24]([Cl:26])=[CH:25][C:20]=1[C:19]2([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[OH:31]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 7748Ethyl bromoacetateHCID 24408BromineHCID 574756367-Bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-one

Product 1

HCID 86658372ethyl 2-(7-bromo-3-chloro-5-hydroxy-5H-chromeno[2,3-c]pyridin-5-yl)acetateYield 104.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

A 3-neck RBF equipped with an addition funnel and reflux condenser was charged with zinc dust (37.9 g, 580 mmol) and diethyl ether (300 ml). Bromine (1.544 ml, 29.0 mmol) was added drop wise to the stirring suspension at RT. After 5 minutes, ethyl 2-bromoacetate (32.3 ml, 290 mmol) was added drop wise via addition funnel over the time period of 1 hour. The reaction mixture was heated to reflux for one hour. 7-Bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-one (30 g, 97 mmol) was added in one portion followed by THF (200 ml). After stirring at 40° C. for 10 minutes, the reaction mixture was cooled to RT and quenched with saturated aqueous ammonium chloride solution (250 mL). The reaction mixture was stirred for 1 hour before diluting with EtOAc and filtering through a pad of celite. The organic layer was separated, washed with brine and dried over MgSO4. The solution was concentrated under reduced pressure to afford ethyl 2-(7-bromo-3-chloro-5-hydroxy-5H-chromeno[2,3-c]pyridin-5-yl)acetate (40.3 g) which was used in the next step without further purification.

Workup

  1. customA 3-neck RBF equipped with an addition funnel
  2. temperaturereflux condenser
  3. additionwise via addition funnel over the time period of 1 hour
  4. temperatureThe reaction mixture was heated
  5. temperatureto reflux for one hour
  6. temperaturethe reaction mixture was cooled to RT
  7. customquenched with saturated aqueous ammonium chloride solution (250 mL)
  8. stirringThe reaction mixture was stirred for 1 hour
  9. additionbefore diluting with EtOAc
  10. filtrationfiltering through a pad of celite
  11. customThe organic layer was separated
  12. washwashed with brine
  13. dry with materialdried over MgSO4
  14. concentrationThe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-ee53226f0bf0433e9094852dac8b9e3b
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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