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

HRID 1966371Notes

Reaction equation

HRID 1966371 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e06bbe93ac8a441da134bf7a25fe55ff
Source dataset
uspto-grants-2013_04
Patent number
US08420645B2

Reaction notes

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