Phosphorus oxychloride → 4-Chloro-2-methyl-10-(2,4,6-trimethylphenyl)pyrido[2,3-b]indolizine

HRID 2299263Notes

Reaction equation

HRID 2299263 reaction equation
O[C:2]1[C:14]2[N:13]3[C:8]([CH:9]=[CH:10][CH:11]=[CH:12]3)=[C:7]([C:15]3[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=3[CH3:23])[C:6]=2[N:5]=[C:4]([CH3:24])[CH:3]=1.P(Cl)(Cl)([Cl:27])=O>>[Cl:27][C:2]1[C:14]2[N:13]3[C:8]([CH:9]=[CH:10][CH:11]=[CH:12]3)=[C:7]([C:15]3[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=3[CH3:23])[C:6]=2[N:5]=[C:4]([CH3:24])[CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178424432HCID 178424432, compound

Product 1

HCID 155132734-Chloro-2-methyl-10-(2,4,6-trimethylphenyl)pyrido[2,3-b]indolizineYield 94%

Procedure

A solution of 4-hydroxy-2-methyl-10-(2,4,6-trimethylphenyl)pyrido-[2,3-b]indolizine (10.1 g; 32 mmol) in phosphorus oxychloride (60 mL) is heated at 100° C. for 1 hour, cooled to room temperature, and concentrated in vacuo. The residue is partitioned into ice water and dichloromethane. The aqueous phase is separated and extracted twice with dichloromethane. The combined organics are washed with a 1 N aqueous sodium hydroxide solution and then with water. The solution is dried (Na2SO4), filtered, and concentrated in vacuo, and the resulting dark residue is filtered through a short pad of silica gel and washed with 25% ethyl acetate in hexane. The filtrate is concentrated in vacuo to give 10.1 g of the title compound as a yellow solid (94%): 1H nmr (400 MHz, CDCl3) d 2.00 (s, 6 H), 2.37 (s, 3 H), 2.64 (s, 3 H), 6.58 (t, 1 H), 6.95 (dd, 1 H), 7.00 (s, 2 H), 7.07 (s, 1 H), 7.08 (d, 1 H), 9.26 (d, 1 H).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue is partitioned into ice water and dichloromethane
  3. customThe aqueous phase is separated
  4. extractionextracted twice with dichloromethane
  5. washThe combined organics are washed with a 1 N aqueous sodium hydroxide solution
  6. dry with materialThe solution is dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. filtrationthe resulting dark residue is filtered through a short pad of silica gel
  10. washwashed with 25% ethyl acetate in hexane
  11. concentrationThe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-dd8b81382aaa4d1ebf00d71a4988b8ba
Source dataset
uspto-grants-2002_12
Patent number
US06495686B2

Reaction notes

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