Potassium Hydroxide → 3-tert-butoxycarbonyl-7-chloro-6-(2-isopropoxy-ethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911470ノート

反応式

HRID 911470 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20]C(=O)N(C)C)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N1CCC2C(SC(=O)N(C)C)=C(Cl)C=C(Cl)C=2CC1)=O)(C)(C)C.[OH-].[K+].I[CH2:55][CH2:56][O:57][CH:58]([CH3:60])[CH3:59]>CO.[Cl-].[NH4+]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:55][CH2:56][O:57][CH:58]([CH3:60])[CH3:59])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 4

HCID 14797Potassium HydroxideHCID 186691542-(2-Iodoethoxy)propaneHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 576562773-tert-butoxycarbonyl-7,9-dichloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

生成物 1

HCID 667068993-tert-butoxycarbonyl-7-chloro-6-(2-isopropoxy-ethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine収率 63%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 25517Ammonium Chloride溶媒2 回

反応条件

温度
57.5 °C

実験手順

To a 4:1 mixture of 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine and 3-tert-butoxycarbonyl-7,9-dichloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (200 mg, 0.52 mmol) in methanol (5 mL) under nitrogen, add potassium hydroxide (0.9 g, 16.1 mmol) at ambient temperature. When the mixture becomes homogenous, heat at 55-60° C. for 2-3 h, until TLC shows the disappearance of starting material. Cool to ambient temperature, add aqueous saturated ammonium chloride, extract three times with diethyl ether, dry over anhydrous MgSO4, and concentrate in vacuo. Dissolve the crude 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine in anhydrous THF (5 mL) under nitrogen and add with stirring 1.0 M potassium t-butoxide in THF (1.0 mL) at ambient temperature. After 10 min, add 2-(2-iodoethoxy)propane (223 mg, 1.04 mmol), and allow the reaction to continue overnight. Dilute with aqueous saturated ammonium chloride, extract the mixture three times with diethyl ether, dry over anhydrous MgSO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (12:1) to provide 3-tert-butoxycarbonyl-7-chloro-6-(2-isopropoxy-ethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a clear oil (127 mg, 63%). Use a method similar to the General Procedure 1-4 to give the title compound as a white solid. MS (ES+) m/z: 300 (M+H)+.

後処理

  1. temperatureCool to ambient temperature
  2. extractionextract three times with diethyl ether
  3. dry with materialdry over anhydrous MgSO4
  4. concentrationconcentrate in vacuo
  5. dissolutionDissolve the crude 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine in anhydrous THF (5 mL) under nitrogen
  6. additionadd
  7. customthe reaction
  8. waitto continue overnight
  9. extractionextract the mixture three times with diethyl ether
  10. dry with materialdry over anhydrous MgSO4
  11. concentrationconcentrate in vacuo
  12. customPurify by chromatography on silica gel eluting with hexane/EtOAc (12:1)

出典と根拠

ORDレコード
ord-445c9ba81cb844deb6213dfc1b5aa7f4
出典データセット
uspto-grants-2011_09
特許番号
US08022062B2

反応ノート

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