Iodoethane → (+/-)-3-tert-butoxycarbonyl-7-chloro-6-(1-cyanopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911540ノート

反応式

HRID 911540 の反応式
[CH:1]([N-]C(C)C)(C)[CH3:2].[Li+].C1CCCCC1.[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][C:26]2[C:29]([S:34][CH2:35][C:36]#[N:37])=[C:30]([Cl:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(I)C>C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][C:26]2[C:29]([S:34][CH:35]([C:36]#[N:37])[CH2:1][CH3:2])=[C:30]([Cl:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

参加物

6

反応物 4

HCID 6340IodoethaneHCID 8078CyclohexaneHCID 2724682Lithium diisopropylamideHCID 667072373-tert-butoxycarbonyl-7-chloro-6-(1-cyano-methylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

生成物 1

HCID 66706966(+/-)-3-tert-butoxycarbonyl-7-chloro-6-(1-cyanopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine収率 68%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

To a stirred solution of 1.5M lithium diisopropylamide in cyclohexane (1.37 mL, 2.05 mmol) in dry THF (5 mL) at −78° C. under dry nitrogen, add a solution of 3-tert-butoxycarbonyl-7-chloro-6-cyanomethylthio-2,3,4,5-tetrahydro-1H-benzo[d]-azepine (600 mg, 1.70 mmol) in THF (5 mL) and continue stirring for 2 h. Rapidly transfer the above solution via cannula to a solution of ethyl iodide (13.2 g, 84.9 mmol) in THF (5 mL) and continue stirring for 1 h. Quench with aqueous saturated ammonium chloride solution, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give (±)-3-tert-butoxycarbonyl-7-chloro-6-(1-cyanopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a pale oil (350 mg, 68%). Use a method similar to the General Procedure 1-4 to give the title compound as an off-white solid. MS (ES+) m/z: 281 (M+H)+.

後処理

  1. stirringcontinue stirring for 1 h
  2. customQuench with aqueous saturated ammonium chloride solution
  3. extractionextract three times with EtOAc
  4. dry with materialdry over anhydrous Na2SO4
  5. concentrationconcentrate in vacuo
  6. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

出典と根拠

ORDレコード
ord-6f218dee2526467c9a1751327560a6e6
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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