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

HRID 75115

반응식

HRID 75115 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
150 °C

실험 절차

(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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-e079e79677014f13803bd2a95da5367b
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835422B2

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