Potassium Iodide → 1-[1-(4-Fluorophenyl)-2-hydroxy-2-quinolin-8-ylethyl]pyrrolidin-2-one

HRID 1170397Notes

Reaction equation

HRID 1170397 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5](Cl)=[O:6].Cl.[NH2:9][CH:10]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[N:21]=[CH:20][CH:19]=[CH:18]2)[OH:12].C(N(CC)CC)C.[OH-].[Na+].[I-].[K+].P([O-])(O)(O)=O.[Na+]>CN(C=O)C>[F:29][C:26]1[CH:25]=[CH:24][C:23]([CH:10]([N:9]2[CH2:2][CH2:3][CH2:4][C:5]2=[O:6])[CH:11]([OH:12])[C:13]2[CH:14]=[CH:15][CH:16]=[C:17]3[C:22]=2[N:21]=[CH:20][CH:19]=[CH:18]3)=[CH:28][CH:27]=1

Participants

8

Reactant 6

HCID 4875Potassium IodideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 783704-Chlorobutyryl chlorideHCID 23672064Monosodium phosphateHCID 675240822-Amino-2-(4-fluorophenyl)-1-quinolin-8-ylethanol hydrochloride

Product 1

HCID 675239451-[1-(4-Fluorophenyl)-2-hydroxy-2-quinolin-8-ylethyl]pyrrolidin-2-oneYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-8 °C

Procedure

0.615 ml (5.18 mmol) of 4-chlorobutyryl chloride (95%) was slowly added dropwise to a solution of 1.5 g (4.7 mmol) of 2-amino-2-(4-fluorophenyl)-1-quinolin-8-ylethanol hydrochloride and 1.96 ml (14.1 mmol) of triethylamine in 15 ml of DMF cooled to −8° C. After stirring at −8 to −10° C. for 1 h, 2.25 g (56.3 mmol) of sodium hydroxide pellets and 156 mg (0.94 mmol) of potassium iodide were added, and the mixture was stirred at room temperature for 3 h. The mixture was poured into an aqueous sodium dihydrogen phosphate solution (80 g/l). Extraction twice with diisopropyl ether was followed by drying over magnesium sulfate. The residue after concentration in vacuo was purified by chromatography with petroleum benzene/ethyl acetate 50:50, then 30:70 to 0:100. 845 mg of 1-[1-(4-fluorophenyl)-2-hydroxy-2-quinolin-8-ylethyl]pyrrolidin-2-one (diastereoisomer A) (yield: 51%) and 127 mg of 1-[1-(4-fluorophenyl)-2-hydroxy-2-quinolin-8-ylethyl]pyrrolidin-2-one (diastereomer B) (yield: 8%) were obtained.

Workup

  1. stirringthe mixture was stirred at room temperature for 3 h
  2. extractionExtraction twice with diisopropyl ether
  3. dry with materialby drying over magnesium sulfate
  4. concentrationThe residue after concentration in vacuo
  5. customwas purified by chromatography with petroleum benzene/ethyl acetate 50:50

Sources & evidence

ORD record
ord-ceae2629aaaa485194202d206a1681a1
Source dataset
uspto-grants-2010_11
Patent number
US07825264B2

Reaction notes

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