Pyridine → Cetilistat

HRID 2265808ノート

反応式

HRID 2265808 の反応式
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].ClC([O-])=O.Cl[C:17]([O:19][CH3:20])=O.N1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(OCC)(=O)C.CCCCC>[CH2:17]([O:19][C:20]1[O:5][C:4](=[O:6])[C:3]2[CH:7]=[C:8]([CH3:11])[CH:9]=[CH:10][C:2]=2[N:1]=1)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:4][CH2:3][CH2:2][CH2:10][CH3:9]

参加物

7

反応物 4

HCID 1049PyridineHCID 6586Methyl chloroformateHCID 762552-Amino-5-methylbenzoic acidHCID 21226386Carbonochloridate

生成物 1

HCID 9952916Cetilistat収率 31%

試薬・触媒・溶媒 2

HCID 8003Pentane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

2-Amino-5-methylbenzoic acid (2.71 g, 17.9 mmol, 0.87 eq.) was dissolved in pyridine (24 ml) and added to the chloroformate solution prepared above. The mixture was stirred at room temperature for 1.75 hours. Methyl chloroformate (13.6 ml, 176 mmol, 8.5 eq) was added slowly, then the mixture was left to stir at ambient temperature overnight. The mixture was diluted with ethyl acetate (20 ml) and washed with water (15 ml) and 10% aqueous citric acid (20 ml). The combined aqueous phases were extracted with ethyl acetate (20 ml). The organic extracts were combined and washed with water (20 ml) and brine (20 ml) then concentrated to give a solid. This was slurried in pentane (5 ml), filtered, then slurried in acetonitrile (5 ml), filtered and purified by flash chromatography on silica (1.5% diisopropylethylamine in dichloromethane) to give a white solid (2.51 g, 31%) δH (400 MHz, CDCl3) 0.87 (3H, t, J 6.8, CH2CH3), 1.24-1.45 (26H, m, 13×CH2), 1.75-1.83 (2H, m, OCH2CH2), 2.41 (3H, s, ArCH3), 4.41 (2H, t, J 6.7, OCH2), 7.30 (1H, d, J 8.3, ArH), 7.51 (1H, dd, J 8.5, 2.0, ArH), 7.90 (1H, d, J 1.1, ArH); m/z (ES+) 402 (MH+); MPt. 72-73° C.

後処理

  1. customprepared above
  2. waitthe mixture was left
  3. stirringto stir at ambient temperature overnight
  4. washwashed with water (15 ml) and 10% aqueous citric acid (20 ml)
  5. extractionThe combined aqueous phases were extracted with ethyl acetate (20 ml)
  6. washwashed with water (20 ml) and brine (20 ml)
  7. concentrationthen concentrated
  8. customto give a solid
  9. filtrationfiltered
  10. filtrationfiltered
  11. custompurified by flash chromatography on silica (1.5% diisopropylethylamine in dichloromethane)

出典と根拠

ORDレコード
ord-5169264421d340b990586f240e5cc02f
出典データセット
uspto-grants-2010_12
特許番号
US07858617B2

反応ノート

読み込み中…