Ammonium Chloride → HCID 21891970, compound

HRID 1007859Notes

Reaction equation

HRID 1007859 reaction equation
Br[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C([O:12][CH2:13][C:14]1[C:15](=[O:35])[N:16]2[C:28](=[CH:29][C:30]=1[C:31](=[O:34])[CH2:32][CH3:33])[C:19]1=[N:20][C:21]3[C:26]([CH:27]=[C:18]1[CH2:17]2)=[CH:25][CH:24]=[CH:23][CH:22]=3)=O.[Cl-].[NH4+]>C1COCC1.[Zn]>[F:8][C:2]([F:9])([C:31]([OH:34])([C:30]1[CH:29]=[C:28]2[N:16]([CH2:17][C:18]3[C:19]2=[N:20][C:21]2[C:26]([CH:27]=3)=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15](=[O:35])[C:14]=1[CH2:13][OH:12])[CH2:32][CH3:33])[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 69585Ethyl bromodifluoroacetate2×HCID 10980947HCID 10980947, compound

Product 1

HCID 21891970HCID 21891970, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Approximately half of a total quantity of ethyl bromodifluoroacetate (1.8 ml, 14 mmol), (9-oxo-7-propionyl-9,11-dihydroindolizino[1,2-b]quinolin-8-yl)methyl formate (2.0 g, 5.75 mmol, as obtained in Stage 1.b.) in suspension in anhydrous THF (10 ml), are added dropwise under argon to a suspension of zinc (1.25 g, 17.2 mmol) in anhydrous THF under reflux (40 ml) then the remaining part of the ethyl bromodifluoroacetate is added. The reaction mixture is maintained under reflux for another half an hour. After cooling down to ambient temperature, the reaction is stopped by the addition of saturated ammonium chloride (20 ml) and the reaction mixture is extracted with dichloromethane (3×20 ml). The combined organic extracts are dried and concentrated. The residue is taken up in diethyl ether (10 ml), filtered and purified by column chromatography (SiO2, CH2Cl2/MeOH:98/2), which produces 664 mg (26%) of product in the form of a yellow solid, m.p. 208-209° C.

Workup

  1. temperatureunder reflux (40 ml)
  2. temperatureThe reaction mixture is maintained
  3. temperatureunder reflux for another half an hour
  4. extractionthe reaction mixture is extracted with dichloromethane (3×20 ml)
  5. customThe combined organic extracts are dried
  6. concentrationconcentrated
  7. filtrationfiltered
  8. custompurified by column chromatography (SiO2, CH2Cl2/MeOH:98/2), which

Sources & evidence

ORD record
ord-65accbc9897141caa68600dc8794d6e6
Source dataset
uspto-grants-2004_09
Patent number
US06797715B1

Reaction notes

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