Chloroform → 1-[2-Chloro-1-hydroxy-3-(6-quinolinyl)propyl]-2,5-pyrrolidinedione

HRID 1396530노트

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HRID 1396530 반응식
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][CH2:12][CH:13]=[O:14])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.N1CCC[C@H]1C(O)=O.Cl[N:24]1[C:28](=[O:29])[CH2:27][CH2:26][C:25]1=[O:30].C(Cl)(Cl)[Cl:32]>C(OCC)(=O)C>[Cl:32][CH:12]([CH2:11][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:1]=[CH:2][CH:3]=[CH:4]2)[CH:13]([N:24]1[C:28](=[O:29])[CH2:27][CH2:26][C:25]1=[O:30])[OH:14]

참가 물질

6

반응물 4

HCID 6212ChloroformHCID 31398ChlorosuccinimideHCID 145742L-ProlineHCID 229313103-(Quinolin-6-yl)propanal

생성물 1

HCID 445128971-[2-Chloro-1-hydroxy-3-(6-quinolinyl)propyl]-2,5-pyrrolidinedione수율 54%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A solution of 3-(quinolin-6-yl)propanal (9, 407 g, 2.2 mol, 1.0 equiv) in chloroform (CHCl3, 1700 mL) was cooled to 0° C. before proline (52 g, 0.44 mol, 0.2 equiv) and N-chlorosuccinimide (NCS, 303 g, 2.31 mol, 1.05 equiv) were added. The resulting reaction mixture was allowed to slowly warm to room temperature (becomes homogeneous) and stirred at room temperature for overnight. The reaction was exothermal to around 40° C. when it reaches room temperature and a precipitate had formed at this point. Once TLC and LC/MS showed that the reaction was deemed complete, the reaction mixture was diluted with ethyl acetate (EtOAc, 1700 mL) and the resulting mixture was cooled to 0° C. The solid was collected by filtration and the collected wet solid cake was placed in a flask and triturated with water (750 mL). The resulting suspension was stirred at room temperature for 30 min before the solids were collected by filtration. The collected solids were washed with water (250 mL) and methyl tert-butyl ether (MTBE, 500 mL) and dried in a vacuum oven at 45° C. to constant weight to afford 1-(2-chloro-1-hydroxy-3-(quinolin-6-yl)propyl)pyrrolidine-2,5-dione (11, 378.7 g, 701.3 g theoretical, 54% yield) as off-white powder. For 11: 1HNMR (DMSO-d6, 400 MHz) δ ppm 8.86 (dd, 1H, J=4.15 Hz, 1.66 Hz), 8.33 (dd, 1H, J=8.51 Hz, 1.04 Hz), 7.98 (d, 1H, J=8.72 Hz), 7.85 (d, 1H, J=1.66 Hz), 7.68 (dd, 1H, J=8.51 Hz, 1.87 Hz), 7.51 (dd, 1H, J=8.29 Hz, 4.15 Hz), 7.36 (d, 1H, J=7.05 Hz), 5.28 (dd, 1H, J=9.54 Hz, 6.85 Hz), 5.07 (dt, 1H, J=9.75 Hz, 2.70 Hz), 3.65 (dd, 1H, J=14.52 Hz, 2.49 Hz), 3.09 (dd, 1H, J=14.52 Hz, 9.75 Hz), 2.64 (s, 4H); C16H15ClN2O3 (MW 318.75), LCMS (EI) m/e 319.2 (M++H).

후처리

  1. additionwere added
  2. customThe resulting reaction mixture
  3. customwas exothermal to around 40° C.
  4. customreaches room temperature
  5. customa precipitate had formed at this point
  6. temperaturethe resulting mixture was cooled to 0° C
  7. filtrationThe solid was collected by filtration
  8. customthe collected wet solid cake was placed in a flask
  9. customtriturated with water (750 mL)
  10. stirringThe resulting suspension was stirred at room temperature for 30 min before the solids
  11. filtrationwere collected by filtration
  12. washThe collected solids were washed with water (250 mL) and methyl tert-butyl ether (MTBE, 500 mL)
  13. customdried in a vacuum oven at 45° C. to constant weight

출처 및 근거

ORD 기록
ord-d6f521f51de643d08c824c26aaa1d5ff
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901123B2

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