Sodium hydride → Benzyl 3-(4-(tert-butoxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

HRID 2363049노트

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HRID 2363049 반응식
[H-].[Na+].[O:3]=[C:4]1[C:8]2([CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:10][CH2:9]2)[N:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:6][NH:5]1.Br[CH2:31][C:32]1[CH:44]=[CH:43][C:35]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:34][CH:33]=1>CN(C)C=O>[C:39]([O:38][C:36]([C:35]1[CH:43]=[CH:44][C:32]([CH2:31][N:5]2[C:4](=[O:3])[C:8]3([CH2:9][CH2:10][N:11]([C:14]([O:16][CH2:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[O:15])[CH2:12][CH2:13]3)[N:7]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:6]2)=[CH:33][CH:34]=1)=[O:37])([CH3:42])([CH3:40])[CH3:41]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 11414578Tert-butyl 4-(bromomethyl)benzoateHCID 58046755Benzyl 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

생성물 1

HCID 58046739Benzyl 3-(4-(tert-butoxycarbonyl)benzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate수율 82.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

Sodium hydride (60% dispersion in oil, 0.46 g, 0.0114 mol) was added portionwise at 0° C. to benzyl 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (4.00 g, 0.0109 mol) in N,N-dimethylformamide (40 mL) and the mixture stirred at 0° C. for 10 minutes. tert-Butyl 4-(bromomethyl)benzoate (3.27 g, 0.0120 mol) was added dropwise at 0° C., the mixture then allowed to warm to room temperature, and stirred for 2 hours. The reaction was quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extracts were washed with brine, dried (MgSO4), and evaporated. The residue was purified by Biotage flash column chromatography (gradient 0 to 30% ethyl acetate/hexanes) to give product as an oil (4.97 g, 82%); 1H NMR (DMSO-d6); 61.53 (s, 9H); 1.72 (d, J=13.6 Hz, 2H); 2.34-2.42 (m, 2H); 3.57 (m, 2H); 3.99-4.03 (m, 2H); 4.61 (s, 2H); 4.63 (s, 2H); 6.69 (d, J=8 Hz, 2H); 6.78 (t, J=7.2 Hz, 1H); 7.18 (dd, J=7.2 Hz and 8.8 Hz, 2H); 7.32-7.39 (m, 5H); 7.42 (d, J=8.4 Hz, 2H); 7.90 (d, J=8.4 Hz, 2H);

후처리

  1. temperatureto warm to room temperature
  2. stirringstirred for 2 hours
  3. customThe reaction was quenched with 2M aqueous hydrochloric acid
  4. extractionextracted with ethyl acetate
  5. washThe ethyl acetate extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue was purified by Biotage flash column chromatography (gradient 0 to 30% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-a36c1a308717455fbb47b0c057761e5e
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691836B2

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