Dimethylformamide → 3-tert-butoxycarbonyl-7-chloro-6-(1-cyano-cyclopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911751노트

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HRID 911751 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22]2[C:25]([S:30][CH2:31][C:32]#[N:33])=[C:26]([Cl:29])[CH:27]=[CH:28][C:21]=2[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].Br[CH2:35][CH2:36]Br.CN(C=O)C>C1(C)C=CC=CC=1>[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22]2[C:25]([S:30][C:31]3([C:32]#[N:33])[CH2:36][CH2:35]3)=[C:26]([Cl:29])[CH:27]=[CH:28][C:21]=2[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 78391,2-DibromoethaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 667072373-tert-butoxycarbonyl-7-chloro-6-(1-cyano-methylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

생성물 1

HCID 667070483-tert-butoxycarbonyl-7-chloro-6-(1-cyano-cyclopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine수율 62.1%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
38 °C

실험 절차

Add sodium bis(trimethylsilyl)amide (5.4 mL, 5.4 mmol, 1M solution in THF) at room temperature under nitrogen to a solution of 3-tert-butoxycarbonyl-7-chloro-6-(1-cyano-methylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (380 mg, 1.1 mmol) in anhydrous toluene (4 mL). Stir the solution for 10 min, then add quickly 1,2-dibromoethane (2.8 mL, 32.4 mmol) followed by anhydrous DMF (4 mL). An exothermic reaction was observed and the reaction temperature increased to 38° C. Stir the mixture for 15 min at ambient temperature, then quench with methanol (2 mL). Concentrate in vacuo and purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to obtain 3-tert-butoxycarbonyl-7-chloro-6-(1-cyano-cyclopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (259 mg).

후처리

  1. customAn exothermic reaction
  2. stirringStir the mixture for 15 min at ambient temperature
  3. customquench with methanol (2 mL)
  4. concentrationConcentrate in vacuo
  5. custompurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

출처 및 근거

ORD 기록
ord-5114de9747134f4595d76051aa3b9ca5
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08022062B2

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