Potassium Hydroxide → 2-(1-(Tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylic acid

HRID 1616063ノート

反応式

HRID 1616063 の反応式
O=[C:2]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[C@@H:3]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH3:4].[F:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25](=[O:30])[C:24]2=O.[OH-:32].[K+]>C(O)C.O>[C:8]([O:7][C:6]([NH:5][CH:3]([C:2]1[C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[C:24]([C:25]([OH:30])=[O:32])[C:23]2[C:27](=[CH:28][CH:29]=[C:21]([F:20])[CH:22]=2)[N:26]=1)[CH3:4])=[O:12])([CH3:11])([CH3:10])[CH3:9]

参加物

5

反応物 3

HCID 14797Potassium HydroxideHCID 2365665-FluoroisatinHCID 58318617(S)-tert-butyl 3-oxo-4-(pyridin-2-yl)butan-2-ylcarbamate

生成物 1

HCID 596346802-(1-(Tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylic acid

試薬・触媒・溶媒 1

HCID 19096565Water ethanol溶媒

反応条件

温度
82 °C

実験手順

(S)-tert-Butyl 3-oxo-4-(pyridin-2-yl)butan-2-ylcarbamate (910 g, 3.44 mol, 1.0 equiv) and 5-fluoroisatin (597 g, 3.62 mol, 1.05 equiv) were dissolved in ethanol/H2O (1:1, 6.0 L each). To this solution was added KOH pellets (609 g, 10.84 mol, 3.15 equiv). The reaction mixture was then heated at 82° C. (internal temperature) overnight. The reaction was monitored using LCMS. Upon completion, the reaction mixture was cooled and evaporated in vacuo to remove ethanol. The aq layer was then washed with DCM (3×4.0 L) and acidified using concd HCl to pH 4. (The acidification procedure was carried out in the following way: The aq layer was taken in a wide mouth flask assembled with mechanical stirrer and pH meter and the flask was cooled using ice-water bath. To this cooled solution was slowly added conc. HCl. To suppress the heat and fumes, small portions of crushed ice was periodically added inside the solution. A yellow solid precipitated out during the addition of conc. HCl). The resultant yellow solid was filtered immediately, thoroughly washed with water (3×1.0 L), triturated with methanol (3×1.0 L), (Note: the product solubility in methanol is very low) then with hexanes (2.0 L), and dried under high vacuum at 60° C. to obtain 2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylic acid as a creamy white solid: 1H NMR (300 MHz, DMSO-d6): δ 1.10 (s, 2H), 1.21 (d, J=6.3 Hz, 3H), 1.30 (s, 7H), 4.82-4.89 (m, 1H), 7.10 (d, J=7.5 Hz, 1H), 7.45-7.49 (m, 1H), 7.56-7.61 (m, 2H), 7.76-7.83 (td, J=3.0 Hz, 1H), 7.93-7.99 (td, J=2.0 Hz, 1H), 8.16-8.21 (m, 1H), 8.71 (d, J=4.8 Hz, 1H); LC-MS (ESI) m/z 412.2 [M+H]+.

後処理

  1. temperatureUpon completion, the reaction mixture was cooled
  2. customevaporated in vacuo
  3. customto remove ethanol
  4. washThe aq layer was then washed with DCM (3×4.0 L)
  5. customThe aq layer was taken in a wide mouth flask
  6. customassembled with mechanical stirrer
  7. temperaturethe flask was cooled
  8. temperatureheat
  9. additionfumes, small portions of crushed ice was periodically added inside the solution
  10. customA yellow solid precipitated out during the addition of conc. HCl)
  11. filtrationThe resultant yellow solid was filtered immediately
  12. washthoroughly washed with water (3×1.0 L)
  13. customtriturated with methanol (3×1.0 L)
  14. customdried under high vacuum at 60° C.

出典と根拠

ORDレコード
ord-6ed09f8707814eae853f27be11387d44
出典データセット
uspto-grants-2014_07
特許番号
US08765768B2

反応ノート

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