Citric Acid → Benzyl 3-(2-(methoxycarbonyl)phenyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

HRID 1751130노트

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HRID 1751130 반응식
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[CH2:8][CH2:7]2)[N:5]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:4][NH:3]1.I[C:29]1[CH:38]=[CH:37][CH:36]=[CH:35][C:30]=1[C:31]([O:33][CH3:34])=[O:32].CNCCNC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(#N)C.[Cu](I)I>[CH3:34][O:33][C:31]([C:30]1[CH:35]=[CH:36][CH:37]=[CH:38][C:29]=1[N:3]1[C:2](=[O:1])[C:6]2([CH2:7][CH2:8][N:9]([C:12]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[O:13])[CH2:10][CH2:11]2)[N:5]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:4]1)=[O:32]

참가 물질

7

반응물 4

HCID 311Citric AcidHCID 8070N,N'-DimethylethylenediamineHCID 69132Benzoic acid, 2-iodo-, methyl esterHCID 58046755Benzyl 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

생성물 1

HCID 66652584Benzyl 3-(2-(methoxycarbonyl)phenyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate수율 61.7%

시약·촉매·용매 2

HCID 83717Copper iodide촉매HCID 6342Acetonitrile용매

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온도
75 °C

실험 절차

A mixture of benzyl 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (2.79 g, 7.63 mmol, 1 equiv), methyl 2-iodobenzoate (2 g, 7.63 mmol, 1 equiv) potassium carbonate (2.11 g, 15.26 mmol, 2 equiv), copper(II) iodide (145.32 mg, 0.763 mmol, 0.1 equiv) and N,N′-dimethyl ethylenediamine (164.25 μl, 1.526 mmol, 0.2 equiv) in acetonitrile was heated at 75° C. for 16 h. Upon cooling 10% citric acid was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated. The residue was purified using the Biotage flash chromatography system (SNAP 100 g cartridge, Rf=0.3, gradient—5%-30% ethyl acetate in hexanes) to afford the title compound as a white powder (2.35 g, 61.57%); 1H NMR (400 MHz, DMSO-d6): δ 1.85 (d, 2H, J=14 Hz); 2.35-2.51 (m, 2H); 3.49 (bs, 2H); 3.98-4.03 (m, 2H); 5.14 (s, 2H); 6.84-6.87 (m, 3H); 7.22-7.26 (m, 2H); 7.32-7.39 (m, 5H); 7.49-7.53 (m, 1H); 7.65 (dd, 1H, J=1.6 and 1.2 Hz); 7.70-7.75 (m, 1H); 7.86 (dd, 1H, J=1.2 and 1.6 Hz); MS for C29H29N3O5 m/z 500.21 (M+H)+.

후처리

  1. additionwas added
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified

출처 및 근거

ORD 기록
ord-77ede1afe8ff4bf8a69be88ac67aa9d9
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156840B2

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