3-[(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)methyl]cyclohexanone → 1-[(3-Phenyl-3-cyclohexenyl)methyl]-4-phenyl-1,2,3,6-tetrahydropyridine

HRID 1034191Notes

Reaction equation

HRID 1034191 reaction equation
[C:1]1([C:7]2[CH2:8][CH2:9][N:10]([CH2:13][CH:14]3[CH2:19][CH2:18][CH2:17][C:16](=O)[CH2:15]3)[CH2:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:21]1([Mg]Br)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1>[C:1]1([C:7]2[CH2:8][CH2:9][N:10]([CH2:13][CH:14]3[CH2:19][CH2:18][CH:17]=[C:16]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:15]3)[CH2:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 117778783-[(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)methyl]cyclohexanoneHCID 178418255HCID 178418255, compound

Product 1

HCID 104492741-[(3-Phenyl-3-cyclohexenyl)methyl]-4-phenyl-1,2,3,6-tetrahydropyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-[(3,6-dihydro-4-phenyl-1(2H)-pyridinyl)methyl]cyclohexanone (Example A) (5.9 g) in 400 mL of tetrahydrofuran is added a solution of phenylmagnesium bromide (9.13 mL, 3.0M in diethyl ether), dropwise under nitrogen, at 0° C. The mixture is stirred at room temperature for 1 hour, then cooled in an ice bath and quenched with 250 mL of 10% aqueous hydrochloric acid solution. The solvent is evaporated in vacuo and the residue partitioned into chloroform/5% aqueous ammonium hydroxide solution. The organic extract is dried over magnesium sulfate and filtered. The filtrate is treated with trifluoroacetic acid (4.2 mL) and stirred overnight at room temperature. The solvent is evaporated in vacuo, and the residue is partitioned into ethyl acetate/5% aqueous ammonium hydroxide solution. The organic extract is dried over magnesium sulfate, filtered, and concentrated. The crude product is purified by medium pressure chromatography to give 3.9 g of (±) -1,2,3,6-tetrahydro-4-phenyl-1-[(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine; mp 90°-95° C. as an off-white solid (Example 1) and 2.7 g of (±)-1,2,3,6-tetrahydro-4-phenyl-1-[(3-phenyl-2-cyclohexen-1-yl)methyl]pyridine; mp 124°-126° C. as a tan solid (Example 1a).

Workup

  1. customat 0° C
  2. temperaturecooled in an ice bath
  3. customquenched with 250 mL of 10% aqueous hydrochloric acid solution
  4. customThe solvent is evaporated in vacuo
  5. customthe residue partitioned into chloroform/5% aqueous ammonium hydroxide solution
  6. extractionThe organic extract
  7. dry with materialis dried over magnesium sulfate
  8. filtrationfiltered
  9. additionThe filtrate is treated with trifluoroacetic acid (4.2 mL)
  10. stirringstirred overnight at room temperature
  11. customThe solvent is evaporated in vacuo
  12. customthe residue is partitioned into ethyl acetate/5% aqueous ammonium hydroxide solution
  13. extractionThe organic extract
  14. dry with materialis dried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe crude product is purified by medium pressure chromatography

Sources & evidence

ORD record
ord-93113b1a39eb4f2ab386e8079ab791cb
Source dataset
uspto-grants-1994_05
Patent number
US05314896

Reaction notes

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