Ammonium Chloride → Ethyl 3-(3-fluoro-2-methylphenyl)-2-azidopropenoate

HRID 650069Notes

Reaction equation

HRID 650069 reaction equation
[O-]CC.[Na+].[F:5][C:6]1[C:7]([CH3:14])=[C:8]([CH:11]=[CH:12][CH:13]=1)[CH:9]=O.[N:15]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N+:16]=[N-:17].[Cl-].[NH4+]>C(O)C.O1CCCC1>[F:5][C:6]1[C:7]([CH3:14])=[C:8]([CH:9]=[C:18]([N:15]=[N+:16]=[N-:17])[C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 69480Acetic acid, azido-, ethyl esterHCID 2723922Sodium ethoxideHCID 27792353-Fluoro-2-methylbenzaldehyde

Product 1

HCID 54359158Ethyl 3-(3-fluoro-2-methylphenyl)-2-azidopropenoateYield 61.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of sodium ethoxide (11.1 g, 163 mmol) in ethanol (100 ml) was cooled to −45° C. and then a solution of 3-fluoro-2-methylbenzaldehyde (9.00 g, 65.2 mmol) and ethyl azidoacetate (21.0 g, 163 mmol) in tetrahydrofuran (30 ml) were slowly added dropwise therein. The reaction temperature of the mixture was raised from −35° C. to −10° C. over 5 hours and the reaction solution was poured in a cooled aqueous ammonium chloride solution. The resulting mixture was extracted with ethyl acetate and the extract was washed with a saturated ammonium chloride solution and then 5% aqueous sodium chloride solution followed by drying over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was treated with silica gel column chromatography (eluated with ethyl acetate/n-hexane=3/97) to give 10.0 g of ethyl 3-(3-fluoro-2-methylphenyl)-2-azidopropenoate.

Workup

  1. temperatureThe reaction temperature of the mixture was raised from −35° C. to −10° C. over 5 hours
  2. extractionThe resulting mixture was extracted with ethyl acetate
  3. washthe extract was washed with a saturated ammonium chloride solution
  4. dry with materialby drying over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. additionthe resulting residue was treated with silica gel column chromatography (eluated with ethyl acetate/n-hexane=3/97)

Sources & evidence

ORD record
ord-96e9b3db961d4b3a8dd526ed7d4adca3
Source dataset
uspto-grants-2001_08
Patent number
US06271251B1

Reaction notes

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