Phosphorus oxychloride → Isopropyl 3-p-fluorobenzoyl-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate

HRID 647996

Reaction equation

HRID 647996 reaction equation
CN(C)[C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1.P(Cl)(Cl)(Cl)=O.[CH:18]1[CH:19]=[CH:20][N:21]2[CH2:26][CH2:25][CH2:24][CH:23]([C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28])[C:22]=12.O.O.O.C([O-])(=O)C.[Na+]>O.ClCCCl>[F:10][C:7]1[CH:6]=[CH:5][C:4]([C:3]([C:20]2[N:21]3[CH2:26][CH2:25][CH2:24][CH:23]([C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28])[C:22]3=[CH:18][CH:19]=2)=[O:11])=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 1410774-fluoro-N,N-dimethylbenzamideHCID 12795102HCID 12795102, compoundHCID 23665404Sodium Acetate Trihydrate

Product 1

HCID 20484013Isopropyl 3-p-fluorobenzoyl-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 962WaterSolvent

Procedure

A solution of 758 mg. of N,N-dimethyl-4-fluorobenzamide and 0.44 ml. of phosphorous oxychloride in 50 ml. of 1,2-dichloroethane is refluxed for one hour. To this solution is added a solution of 500 mg. of isopropyl 5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate in 10 ml. 1,2-dichloroethane. The reaction mixture is refluxed for 3 hours. A solution of 3.3 g. sodium acetate trihydrate in 9 ml water is added and refluxed for a further 10 hours. The organic phase is separated, washed with saturated sodium chloride solution, dried over sodium sulfate and evaporated to dryness. The residue is purified by preparative t.l.c. using hexane:ethyl acetate (90:10). Crystallization from dichloromethane-hexane yields isopropyl 3-p-fluorobenzoyl-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate (XI, R=H, L=p-F, R2 =iC3H7, n=1), m.p. 92° C.

Workup

  1. additionTo this solution is added a solution of 500 mg
  2. temperatureThe reaction mixture is refluxed for 3 hours
  3. temperaturerefluxed for a further 10 hours
  4. customThe organic phase is separated
  5. washwashed with saturated sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. customevaporated to dryness
  8. customThe residue is purified by preparative t.l.c
  9. customCrystallization from dichloromethane-hexane

Sources & evidence

ORD record
ord-cc16e4974dda462b8218d8903d8cfca0
Source dataset
uspto-grants-1983_10
Patent number
US04410534

Linked notes

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