Pyridine → Isopropyl 5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate

HRID 2353861Notes

Reaction equation

HRID 2353861 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][C:4](=[O:8])[C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]1=2.N1C=CC=CC=1.[CH:19]([O:22][C:23](Cl)=[O:24])([CH3:21])[CH3:20]>ClCCl>[CH:19]([O:22][C:23]([N:1]1[CH2:7][CH2:6][CH2:5][C:4](=[O:8])[C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]1=2)=[O:24])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7917Isopropyl chloroformateHCID 2947881,2,3,4-Tetrahydro-benzo(b)azepin-5-one

Product 1

HCID 68680367Isopropyl 5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled (0° C.) solution of 1,2,3,4-Tetrahydro-benzo[b]azepin-5-one (1.5 g, 9.3 mmol) and pyridine (2.26 ml, 27.9 mmol) in dichloromethane (30 ml) was added 1M isopropylchloroformate (solution in toluene) dropwise over 10 minutes. After addition was completed, the mixture was removed from the cold bath and stirred for 18 hours at room temperature. The mixture was cooled to 0° C., then treated with aqueous 1N NaOH and stirred for 30 minutes. After layer separation, the aqueous layer was extracted with dichloromethane. The combined organic phases were washed with 1N HCl, saturated aqueous NaHCO3, brine, then dried (Na2SO4) and concentrated to an oil. Purification by silica gel chromatography (eluent, 3:1 n-hexanes:ethyl acetate) provided 5-Oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (1.91 g).

Workup

  1. additionAfter addition
  2. customthe mixture was removed from the cold bath
  3. temperatureThe mixture was cooled to 0° C.
  4. additiontreated with aqueous 1N NaOH
  5. stirringstirred for 30 minutes
  6. customAfter layer separation
  7. extractionthe aqueous layer was extracted with dichloromethane
  8. washThe combined organic phases were washed with 1N HCl, saturated aqueous NaHCO3, brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated to an oil
  11. customPurification by silica gel chromatography (eluent, 3:1 n-hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-92c4e69867ef4cbf8ec6578f77668030
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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