Chloroform → 1-[2-Chloro-1-hydroxy-2-(1-quinolin-6-ylcyclopropyl)ethyl]pyrrolidine-2,5-dione
Reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3([CH2:14][CH:15]=[O:16])[CH2:13][CH2:12]3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.N1CCC[C@@H]1C(O)=O.Cl[N:26]1[C:30](=[O:31])[CH2:29][CH2:28][C:27]1=[O:32].C(Cl)(Cl)[Cl:34]>>[Cl:34][CH:14]([C:11]1([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[N:1]=[CH:2][CH:3]=[CH:4]3)[CH2:12][CH2:13]1)[CH:15]([N:26]1[C:30](=[O:31])[CH2:29][CH2:28][C:27]1=[O:32])[OH:16]Participants
Conditions
- Temperature
- 0 °C
Procedure
To a cooled (0° C.) mixture of (1-quinolin-6-ylcyclopropyl)acetaldehyde (9.9 g, 47 mmol), D-proline (1.1 g, 9.4 mmol) in chloroform (200 mL) was added N-chlorosuccinimide (6.26 g, 46.9 mmol). The mixture was stirred at 0° C. for 30 min and then gradually warmed to RT for 2 h. The reaction mixture was quenched with saturated sodium bicarbonate (25 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The precipitate formed was filtered to give the desired product. The filtrate was chromatographed on silica gel with EtOAc in methylene chloride (10%) to afford chloro(1-quinolin-6-ylcyclopropyl)acetaldehyde which was contaminated with pyrrolidine-2,5-dione (13.0 g), and automatically converted to the desired product after a few days. The total desired product obtained is 16 g. LCMS: (M+H)=345.0/347.0.
Workup
- temperatureTo a cooled
- temperaturegradually warmed to RT for 2 h
- customThe reaction mixture was quenched with saturated sodium bicarbonate (25 mL)
- extractionextracted with EtOAc (3×100 mL)
- washThe combined organic layers were washed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe precipitate formed
- filtrationwas filtered
Sources & evidence
- ORD record
- ord-98422e5cbc414002bf435dfff8081167
- Source dataset
- uspto-grants-2013_06
- Patent number
- US08461330B2
Reaction notes
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