Pyridine → Cetilistat

HRID 1169575노트

반응식

HRID 1169575 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

HCID 9952916Cetilistat수율 31%

시약·촉매·용매 2

HCID 8003Pentane용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-aaabe8ca53394d9d8ae3c24c9a513dac
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07825113B2

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