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

HRID 911540노트

반응식

HRID 911540 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-6f218dee2526467c9a1751327560a6e6
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08022062B2

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