Sodium Azide → HCID 86701270、化合物

HRID 2276071ノート

反応式

HRID 2276071 の反応式
[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][CH2:17]OS(C)(=O)=O)[C:14](=[O:23])[O:13][CH2:12][C@H:11]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:10](=[O:32])[O:9][C@H:8]1[CH3:33])(=[O:5])[CH:2]([CH3:4])[CH3:3].[N-:34]=[N+:35]=[N-:36].[Na+].[Cl:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([C:45]#[CH:46])[CH:40]=1.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CN(C=O)C.[O-]S([O-])(=O)=O.[Cu+2]>[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][CH2:17][N:34]2[CH:46]=[C:45]([C:41]3[CH:42]=[CH:43][CH:44]=[C:39]([Cl:38])[CH:40]=3)[N:36]=[N:35]2)[C:14](=[O:23])[O:13][CH2:12][C@H:11]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:26])[C:10](=[O:32])[O:9][C@H:8]1[CH3:33])(=[O:5])[CH:2]([CH3:4])[CH3:3]

参加物

7

反応物 4

HCID 33557Sodium AzideHCID 1230861-Chloro-3-ethynylbenzeneHCID 23667548Sodium AscorbateHCID 86701267HCID 86701267、化合物

生成物 1

HCID 86701270HCID 86701270、化合物収率 64.8%

試薬・触媒・溶媒 2

HCID 24462Copper Sulfate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

To a solution (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-6-methyl-8-(2(methylsulfonyloxy)ethyl)-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (140 mg, 0.28 mmol) in DMF (3 mL) at room temperature (about 22° C.) was added NaN3 (37 mg, 0.57 mmol). The resulting reaction mixture was heated to 60° C. and stirred for 3 h. The reaction was partitioned between sat'd aqueous NaHCO3 solution (20 mL) and EtOAc (25 mL) and the phases were separated. The aqueous phase was extracted with additional EtOAc (2×25 mL), and the combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated to dryness. The crude residue was dissolved in DMF/H2O (1 mL/1 mL) and the resulting solution was treated with 1-chloro-3-ethynylbenzene (39 mg, 0.28 mol), CuSO4 (4 mg, 0.025 mmol), and sodium ascorbate (22 mg, 0.11 mmol), and the reaction mixture was stirred at room temperature overnight. The reaction was partitioned between sat'd aqueous NaHCO3 solution (15 mL) and EtOAc (20 mL) and the phases were separated. The aqueous phase was extracted with additional EtOAc (2×20 mL), and the combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated to dryness. The crude residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient) to afford the title compound (105 mg, 64%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.82 (d, J=1.7 Hz, 1H), 7.70 (dq, J=3.2, 1.5 Hz, 2H), 7.33 (ddd, J=10.9, 8.0, 4.9 Hz, 2H), 5.40-5.15 (m, 2H), 5.08 (t, J=9.8 Hz, 1H), 4.82 (dd, J=14.6, 4.8 Hz, 2H), 4.51-4.24 (m, 2H), 3.63 (s, 1H), 2.66-2.49 (m, 2H), 2.42-2.25 (m, 1H), 2.14-2.00 (m, 1H), 1.45 (s, 9H), 1.27 (dd, J=6.7, 1.3 Hz, 3H), 1.18 (d, J=7.1 Hz, 6H); ESIMS m/z 579 ([M+H]+).

後処理

  1. customThe resulting reaction mixture
  2. customThe reaction was partitioned between sat'd aqueous NaHCO3 solution (20 mL) and EtOAc (25 mL)
  3. customthe phases were separated
  4. extractionThe aqueous phase was extracted with additional EtOAc (2×25 mL)
  5. dry with materialthe combined EtOAc extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. dissolutionThe crude residue was dissolved in DMF/H2O (1 mL/1 mL)
  9. stirringthe reaction mixture was stirred at room temperature overnight
  10. customThe reaction was partitioned between sat'd aqueous NaHCO3 solution (15 mL) and EtOAc (20 mL)
  11. customthe phases were separated
  12. extractionThe aqueous phase was extracted with additional EtOAc (2×20 mL)
  13. dry with materialthe combined EtOAc extracts were dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated to dryness
  16. customThe crude residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient)

出典と根拠

ORDレコード
ord-56b18bf5fad54f2096d15655414640cd
出典データセット
uspto-grants-2015_09
特許番号
US09131690B2

反応ノート

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