Sodium hydride → 3-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670547노트

반응식

HRID 1670547 반응식
[H-].[Na+].[S:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[SH:8].[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([CH2:28]Cl)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C.[I-].[K+]>[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([CH2:28][S:8][C:4]3[S:3][CH:7]=[CH:6][CH:5]=3)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 5226742-ThiophenethiolHCID 597874103-tert-Butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

생성물 1

HCID 673359353-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine수율 70.6%

시약·촉매·용매 2

HCID 4875Potassium Iodide촉매HCID 6228Dimethylformamide용매2회

반응 조건

온도
45 °C

실험 절차

Suspend sodium hydride (20 mg, 60% dispersion in mineral oil) in anhydrous DMF (2 mL) and add thiophene-2-thiol (35 mg, 0.38 mmol) at room temperature. After 5 min add 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (150 mg, 0.38 mmol) and catalytic potassium iodide (1 mg) in anhydrous DMF (1 mL) and stir at 45° C. for 13 h. Cool the mixture to room temperature and partition between brine and EtOAc. Dry the organic layer over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 7:3 gradient) to give 3-tert-butoxycarbonyl-7-chloro-6-(thiophen-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (110 mg).

후처리

  1. temperatureCool the mixture to room temperature
  2. custompartition between brine and EtOAc
  3. dry with materialDry the organic layer over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 7:3 gradient)

출처 및 근거

ORD 기록
ord-e06239ab55a142d59a6d140e0a7ec016
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994163B2

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