Ammonium Chloride → HCID 21906846, compound

HRID 1244723Notes

Reaction equation

HRID 1244723 reaction equation
C[O-].[Na+].[Cl:4][C:5]1[CH:6]=[C:7]([CH:10]=O)[S:8][CH:9]=1.[N:12]([CH2:15][C:16]([O:18][CH3:19])=[O:17])=[N+]=[N-].[Cl-].[NH4+]>CO>[Cl:4][C:5]1[C:6]2[NH:12][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:10][C:7]=2[S:8][CH:9]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 4020482Methyl 2-azidoacetateHCID 10942334Sodium MethoxideHCID 109971824-chlorothiophene-2-carbaldehyde

Product 1

HCID 21906846HCID 21906846, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
-25 °C

Procedure

Methanolic sodium methoxide solution (28%) (5 ml, 25.9 mmol) was diluted with MeOH (5 ml) and was cooled to −25° C. under nitrogen. A solution of 4-chloro-2-thiophenecarboxaldehyde (J Heterocyclic Chem, 1976, 13, 393; 1.1 g, 7.5 mmol) and methyl azidoacetate (3.0 g, 26.1 mmol) in MeOH (20 ml) was added dropwise, maintaining the temperature at −25° C. On completion of addition the solution was allowed to warm to 5° C. over a period of approximately 16 hours. The solution was added to saturated aqueous ammonium chloride (250 ml) and the mixture was extracted using DCM. The combined organic layers were concentrated at 0° C. The residue was taken up in xylene (30 ml) and this solution was added dropwise to xylene (120 ml) under reflux. The solution was heated under reflux for 30 minutes before being cooled and concentrated. The title compound was purified by a mixture of crystallisation (EtOAc/isohexane) and chromatography on a Bond Elut column eluting with a graduated solvent of 5–50% EtOAc in isohexane (640 mg, 40%). NMR (CDCl3) 9.1 (1H, br), 7.1 (2H, s), 3.9 (3H, s); m/z 214.3.

Workup

  1. temperaturemaintaining the temperature at −25° C
  2. additionOn completion of addition the solution
  3. temperatureto warm to 5° C. over a period of approximately 16 hours
  4. extractionthe mixture was extracted
  5. concentrationThe combined organic layers were concentrated at 0° C
  6. additionthis solution was added dropwise to xylene (120 ml)
  7. temperatureunder reflux
  8. temperatureThe solution was heated
  9. temperatureunder reflux for 30 minutes
  10. temperaturebefore being cooled
  11. concentrationconcentrated
  12. customThe title compound was purified by a mixture of crystallisation (EtOAc/isohexane) and chromatography on a Bond Elut column
  13. washeluting with a graduated solvent of 5–50% EtOAc in isohexane (640 mg, 40%)

Sources & evidence

ORD record
ord-d6b20170f36e4085a4997b5f23e0b672
Source dataset
uspto-grants-2006_10
Patent number
US07122567B2

Reaction notes

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