1,2-Dichloroethane → 3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxylic acid

HRID 75115

Reaction equation

HRID 75115 reaction equation
CO[C:3]1[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]=1.[C:10]1([C:16]2[O:17][C:18](=[O:21])[CH2:19][N:20]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.ClCCCl.O.[OH-].[Li+]>C1COCC1.O>[C:10]1([C:16]2[N:9]3[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]3=[C:19]([C:18]([OH:21])=[O:17])[N:20]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 65073AzlactoneHCID 756572H-Azepine, 3,4,5,6-tetrahydro-7-methoxy-HCID 168937Lithium hydroxide, monohydrate

Product 1

HCID 253421753-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

(E)-7-methoxy-3,4,5,6-tetrahydro-2H-azepine (0.395 g, 3.10 mmol) and 2-phenyloxazol-5(4H)-one (0.5 g, 3.10 mmol) were dissolved together in THF (2 mL) and DCE (2 mL) in a 5 mL microwave vial to give a orange solution. The vial was sealed and the solution was heated to 150° C. for 5 minutes. LCMS showed two peaks of the same mass (tautomers of the condensation product, Rf 0.78 and 0.83 minutes, respectively). The reaction was concentrated and the residue diluted with MeOH (1 mL) and a solution of lithium hydroxide monohydrate (0.391 g, 9.31 mmol) in water (0.5 mL). The reaction was subjected to microwave irradiation and heated at 120° C. for 5 minutes. LCMS showed a single, new peak (Rf0.53 same molecular weight) corresponding to the desired product. The reaction was concentrated to remove MeOH and then diluted with water (1 mL). The solution was acidified to pH 2 with 5M HCl and extracted with of DCM (3×2 mL). The combined organic layers were filter, dried over anhydrous sodium sulfate and evaporated under reduced pressure to provide 3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxylic acid (421 mg, 59%) as a brown oil that was used without further purification. LCMS (+ESI) m/z 257.1 [M+H]+.

Workup

  1. customThe vial was sealed
  2. customtautomers of the condensation product, Rf 0.78 and 0.83 minutes
  3. concentrationThe reaction was concentrated
  4. additionthe residue diluted with MeOH (1 mL)
  5. customirradiation
  6. temperatureheated at 120° C. for 5 minutes

Sources & evidence

ORD record
ord-e079e79677014f13803bd2a95da5367b
Source dataset
uspto-grants-2014_09
Patent number
US08835422B2

Linked notes

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