4-Toluenesulfonyl chloride → HCID 178427792, 화합물

HRID 353917노트

반응식

HRID 353917 반응식
[N+:1]([C:4]1[N:5]=[CH:6][N:7]([CH:9]2[CH2:12][CH:11]([OH:13])[CH2:10]2)[CH:8]=1)([O-:3])=[O:2].CCN(CC)CC.[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>C(Cl)Cl>[N+:1]([C:4]1[N:5]=[CH:6][N:7]([C@H:9]2[CH2:10][C@H:11]([O:13][S:27]([C:24]3[CH:25]=[CH:26][C:21]([CH3:31])=[CH:22][CH:23]=3)(=[O:29])=[O:28])[CH2:12]2)[CH:8]=1)([O-:3])=[O:2]

참가 물질

5

반응물 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 220259763-(4-Nitro-1H-imidazol-1-yl)cyclobutan-1-ol

생성물 1

HCID 178427792HCID 178427792, 화합물수율 37%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

3-(4-nitro-imidazol-1-yl)-cyclobutanol (Preparation 4, Step 1; 4 g, 22 mmol) was treated with Et3N (7.7 mL, 55 mmol) in methylene chloride (150 mL) followed by p-toluenesulfonyl chloride (TsCl) (5 g, 26.4 mmol) and 4-N,N-dimethylaminopyridine (DMAP) (268 mg, 2.2 mmol). The resulting mixture was stirred at room temperature for 24 h. Analysis by thin layer chromatography showed two new spots. The reaction mixture was diluted with methylene chloride and was washed with water (1×) and brine (1×). The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. Purification by silica gel chromatography (1:1 to 2:1 hexanes-ethyl acetate) allowed for separation of the trans and cis diastereomers. The first spot to elute (high Rf) was the trans-isomer, trans-toluene-4-sulfonic acid 3-(4-nitro-imidazol-1-yl)-cyclobutyl ester (2.7 g, 37% yield); 1H NMR (400 MHz, CDCl3) δ7.79 (s, 1H), 7.77 (m, 2H), 7.44 (d, J=1.7 Hz, 1H), 7.36 (dd, J=0.5, 8.0 Hz, 2H), 5.034 (m, 1H), 4.94 (m, 1H), 2.9 (m, 2H), 2.7 (m, 2H); MS (AP/Cl): 338.1 (M+H)+. The second spot to elute was the cis-isomer, cis-toluene-4-sulfonic acid 3-(4-nitro-imidazol-1-yl)-cyclobutyl ester (2.9 g, 39% yield); 1H NMR (400 MHz, CDCl3) δ7.8 (m, 3H), 7.43 (d, J=1.4 Hz, 1H), 7.36 (dd, J=0.6, 8.5 Hz, 2H), 4.74 (m, 1H), 4.30 (m, 1H), 3.05 (m, 2H), 2.6-2.5 (m, 2H), 2.45 (s, 3H); MS (AP/Cl): 338.1 (M+H)+. Relative configurations were determined by the measurement of nuclear Overhauser effects.

후처리

  1. washwas washed with water (1×) and brine (1×)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by silica gel chromatography (1:1 to 2:1 hexanes-ethyl acetate)
  6. customallowed for separation of the trans and cis diastereomers
  7. washThe first spot to elute (high Rf)

출처 및 근거

ORD 기록
ord-2750cf7bb0054fa19534a756a67c334c
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06756385B2

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