Phosphorus oxychloride → isopropyl 3-(N-methyl-2-pyrroyl)-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate

HRID 648014Notes

Reaction equation

HRID 648014 reaction equation
CN(C)[C:3]([C:5]1[N:6]([CH3:10])[CH:7]=[CH:8][CH:9]=1)=[O:4].P(Cl)(Cl)(Cl)=O.[CH:17]1[CH:18]=[CH:19][N:20]2[CH2:25][CH2:24][CH2:23][CH:22]([C:26]([O:28][CH:29]([CH3:31])[CH3:30])=[O:27])[C:21]=12.C([O-])(=O)C.[Na+]>O.ClCCCl.ClCCl>[CH3:10][N:6]1[CH:7]=[CH:8][CH:9]=[C:5]1[C:3]([C:19]1[N:20]2[CH2:25][CH2:24][CH2:23][CH:22]([C:26]([O:28][CH:29]([CH3:31])[CH3:30])=[O:27])[C:21]2=[CH:17][CH:18]=1)=[O:4]

Participants

8

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 12779822N,N,1-trimethyl-1H-pyrrole-2-carboxamideHCID 12795102Isopropyl 5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate

Product 1

HCID 70534455isopropyl 3-(N-methyl-2-pyrroyl)-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1.40 g. of N,N-dimethyl-1-methylpyrrole-2-carboxamide in 30 ml. of anhydrous dichloromethane containing 1.53 g. of phosphorous oxychloride is refluxed for 30 minutes under an argon atmosphere. To this solution is added a solution of 895 mg. of isopropyl 5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate in 20 ml. of 1,2-dichloroethane. The reaction mixture is refluxed under an argon atmosphere for 50 hours, cooled to room temperature and treated with a solution of 4.1 g. of sodium acetate dissolved in 15 ml. of water. The resultant mixture is refluxed for 30 minutes further, and then cooled, the organic phase is separated and the aqueous phase extracted with chloroform. The combined organic solutions are washed with saturated sodium chloride solution (2×10 ml.), dried with anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The oily residue is purified by t.l.c. using ethyl acetate:methylene chloride as eluant, to yield isopropyl 3-(N-methyl-2-pyrroyl)-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate (XIV, R=H, Q=CH 3, R2 =iC3H7, n=1).

Workup

  1. additionTo this solution is added a solution of 895 mg
  2. temperatureThe reaction mixture is refluxed under an argon atmosphere for 50 hours
  3. additiontreated with a solution of 4.1 g
  4. temperaturecooled
  5. customthe organic phase is separated
  6. extractionthe aqueous phase extracted with chloroform
  7. washThe combined organic solutions are washed with saturated sodium chloride solution (2×10 ml.)
  8. dry with materialdried with anhydrous sodium sulfate
  9. customevaporated to dryness under reduced pressure
  10. customThe oily residue is purified by t.l.c

Sources & evidence

ORD record
ord-92d91e883a784efe9f98f78a5ed968a6
Source dataset
uspto-grants-1983_10
Patent number
US04410534

Reaction notes

Loading…