Methyl chloroformate → HCID 22219595, compound

HRID 488378Notes

Reaction equation

HRID 488378 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[CH2:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][CH2:9][NH:8][CH2:7]1.C(=O)(O)[O-].[Na+].[N+:22]([O-])([O-:24])=[O:23].[NH4+]>C1COCC1.O.S(=O)(=O)(O)O>[N+:22]([C:14]1[CH:15]=[CH:16][C:11]2[CH2:10][CH2:9][N:8]([C:2]([O:4][CH3:5])=[O:3])[CH2:7][CH2:6][C:12]=2[CH:13]=1)([O-:24])=[O:23]

Participants

8

Reactant 4

HCID 6586Methyl chloroformateHCID 22985Ammonium nitrateHCID 516892Sodium BicarbonateHCID 14002432,3,4,5-Tetrahydro-1H-benzo(d)azepine

Product 1

HCID 22219595HCID 22219595, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1118Sulfuric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl chloroformate (120 mL, 1.53 mol) is added dropwise to 2,3,4,5-tetrahydro-1H-3-benzazepine (J. Heterocyclic Chem., 1971, 779-783) in THF (1 L), water (1 L), and sodium bicarbonate (206 g, 2.46 mmol) at 0° C. The mixture is stirred at room temperature for 4 h, extracted with dichloromethane which is washed with 1 N hydrochloric acid, water, 1 N sodium hydroxide, and brine then dried over anhydrous sodium sulfate, filtered, and concentrated to a amber oil which slowly crystallized. The solid is dissolved in concentrated sulfuric acid (500 mL), cooled to −10° C., and treated dropwise with a solution of ammonium nitrate (82 g, 1.03 mol) in concentrated sulfuric acid (500 mL). The temperature is maintained at 0-5° C. for 3 h then poured onto ice and extracted with dichloromethane. The organic layer is washed with water, saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, concentrated, and chromatographed on a Chiralcel® AD column with 20% isopropanol in heptane to give 161 g (66%) of the title compound.

Workup

  1. extractionextracted with dichloromethane which
  2. washis washed with 1 N hydrochloric acid, water, 1 N sodium hydroxide, and brine
  3. dry with materialthen dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a amber oil which
  6. customslowly crystallized
  7. dissolutionThe solid is dissolved in concentrated sulfuric acid (500 mL)
  8. temperaturecooled to −10° C.
  9. temperatureThe temperature is maintained at 0-5° C. for 3 h
  10. additionthen poured onto ice
  11. extractionextracted with dichloromethane
  12. washThe organic layer is washed with water, saturated aqueous sodium bicarbonate
  13. dry with materialdried over anhydrous sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customchromatographed on a Chiralcel® AD column with 20% isopropanol in heptane

Sources & evidence

ORD record
ord-66962bf5cfa24783b8d9033154964cac
Source dataset
uspto-grants-2005_12
Patent number
US06972286B2

Reaction notes

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