Phosphoric Acid → 5-Phenyl-3-[1-(phenylmethyl)-1,2,3,6-tetrahydro-4-pyridinyl]-1H-indole-7-carboxamide

HRID 2267483Notes

Reaction equation

HRID 2267483 reaction equation
P(=O)(O)(O)O.[CH2:6]([N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][C:14]1=O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:20]1([C:26]2[CH:27]=[C:28]3[C:32](=[C:33]([C:35]([NH2:37])=[O:36])[CH:34]=2)[NH:31][CH:30]=[CH:29]3)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(O)(=O)C>[C:20]1([C:26]2[CH:27]=[C:28]3[C:32](=[C:33]([C:35]([NH2:37])=[O:36])[CH:34]=2)[NH:31][CH:30]=[C:29]3[C:16]2[CH2:15][CH2:14][N:13]([CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:18][CH:17]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 1004Phosphoric AcidHCID 51700761-Benzyl-2-piperidoneHCID 112070915-phenyl-1H-indole-7-carboxamide

Product 1

HCID 114525415-Phenyl-3-[1-(phenylmethyl)-1,2,3,6-tetrahydro-4-pyridinyl]-1H-indole-7-carboxamide

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
90 °C

Procedure

To a 5 L three necked flask was charged 85% wt Phosphoric acid (423 mL, 6.16 moles, 25 eq), benzyl piperidone (142 mL, 0.733 mole, 3 eq) and glacial acetic acid (400 mL). The resulting mixture was heated to 90° C. A solution of 5-phenyl-1H-indole-7-carboxamide (57.69 g, 0.244 mole, 1 eq) in glacial acetic acid (755 mL) was then added portionwise. The reaction was then maintained at 90° C. overnight. The reaction mixture was cooled to room temperature. It was then divided into two equal portions and each was added slowly to separate stirring mixtures of ice/0.88 ammonia (1 L/1 L). A dry ice/acetone bath was also used to control the exotherm. Ethyl acetate (600 mL) was then added to the mixture with stirring. It was then filtered and the solid washed well with ethyl acetate. The filtrate was then separated and the aq was re-extracted with ethyl acetate. The organics were then dried over magnesium sulfate and filtered before the two batches were combined and evaporated under reduced pressure. The residue was then dissolved in 3% (3.5M ammonia in methanol) in DCM (300 mL). The solid precipitate was then collected by filtration and was then dried in vacuo to yield the desired product. (42.25 g) MS: (M+H): 408.

Workup

  1. temperatureThe reaction was then maintained at 90° C. overnight
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additioneach was added slowly
  4. customto separate
  5. customA dry ice/acetone bath was also used
  6. additionEthyl acetate (600 mL) was then added to the mixture
  7. stirringwith stirring
  8. filtrationIt was then filtered
  9. washthe solid washed well with ethyl acetate
  10. customThe filtrate was then separated
  11. extractionthe aq was re-extracted with ethyl acetate
  12. dry with materialThe organics were then dried over magnesium sulfate
  13. filtrationfiltered before the two batches
  14. customevaporated under reduced pressure
  15. dissolutionThe residue was then dissolved in 3% (3.5M ammonia in methanol) in DCM (300 mL)
  16. filtrationThe solid precipitate was then collected by filtration
  17. customwas then dried in vacuo

Sources & evidence

ORD record
ord-0de541a38141431ebd64ef5595c325a6
Source dataset
uspto-grants-2010_12
Patent number
US07858796B2

Reaction notes

Loading…