Phenol → HCID 9837365, compound

HRID 981966Notes

Reaction equation

HRID 981966 reaction equation
[CH2:1]([NH:4][N:5]1[CH2:9][CH2:8][CH2:7][C:6]1=[O:10])[CH2:2][CH3:3].Cl.Cl[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.C1(O)C=CC=CC=1>ClCCl>[CH2:1]([N:4]([C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[N:5]1[CH2:9][CH2:8][CH2:7][C:6]1=[O:10])[CH2:2][CH3:3]

Participants

5

Reactant 3

HCID 996PhenolHCID 818524-Chloropyridine hydrochloride2×HCID 17854009HCID 17854009, compound

Product 1

HCID 9837365HCID 9837365, compoundYield 39.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
143 °C

Procedure

A slurry consisting of 1-(propylamino)-2-pyrrolidinone (7.96 g), 4-chloropyridine hydrochloride (6.31 g) and phenol (20.9 g) was heated in a 143° C. oil bath under nitrogen. After 30 min., the resulting solution was treated with additional 4-chloropyridine hydrochloride (6.30 g) and heated for an additional 30 minutes. The mixture was cooled to room temperature and diluted with dichloromethane. The organic layer was washed with dilute aqueous sodium bicarbonate and the combined aqueous layers back-extracted with dichloromethane and ether. The combined organic layers were washed with brine and dried (K2CO3). Filtration, concentration, and purification via flash column chromatography (silica gel, 10% MeOH/DCM) and preparative HPLC afforded 3.65 g (30%) of 1-(propyl-4-pyridinylamino)-2-pyrrolidinone as an oil. The oxalate was prepared with 1.0 eq. oxalic acid in absolute ethanol, m.p. 194°-195.5° C.

Workup

  1. temperatureheated for an additional 30 minutes
  2. temperatureThe mixture was cooled to room temperature
  3. washThe organic layer was washed with dilute aqueous sodium bicarbonate
  4. extractionthe combined aqueous layers back-extracted with dichloromethane and ether
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (K2CO3)
  7. filtrationFiltration, concentration, and purification via flash column chromatography (silica gel, 10% MeOH/DCM) and preparative HPLC

Sources & evidence

ORD record
ord-188ddce726494b159186a158197a084e
Source dataset
uspto-grants-1991_02
Patent number
US04994472

Reaction notes

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