Oxygen → (R)-alpha-(2-pyridyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol

HRID 1721123Notes

Reaction equation

HRID 1721123 reaction equation
O=O.[F:3][C:4]([F:28])([F:27])[C:5]1[CH:14]=[C:13]([C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[O:16])[C:12]2[C:7](=[C:8]([C:23]([F:26])([F:25])[F:24])[CH:9]=[CH:10][CH:11]=2)[N:6]=1>C1(C)C=CC=CC=1>[N:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C@@H:15]([C:13]1[C:12]2[C:7](=[C:8]([C:23]([F:24])([F:25])[F:26])[CH:9]=[CH:10][CH:11]=2)[N:6]=[C:5]([C:4]([F:28])([F:3])[F:27])[CH:14]=1)[OH:16]

Participants

4

Reactant 2

HCID 977OxygenHCID 995123935853-55-5

Product 1

HCID 11257265(R)-alpha-(2-pyridyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanolYield 92%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A 500 ml autoclave was loaded in a glove box (O2 content<1 ppm) with 14.8 g (40 mmol) of 2-pyridyl 2,8-bis(trifluoromethyl)-4-quinolyl ketone, with the catalyst solution prepared above and with 134 ml of toluene. The hydrogenation was carried out at 60°, at a constant pressure of 60 bar H2 and while stirring intensively. After a hydrogenation time of 19 hours the conversion was 100° (TLC). The hydrogenation solution was evaporated on a rotary evaporator at 45°/20 mbar. For the crystallization of the product, the residue (13.8 g) was dissolved in 21 ml of hot toluene, cooled slowly to RT and stirred for 16 hours. The crystallization was completed by cooling to 1° and stirring for 3 hours. The yellow crystals were filtered off, washed with cold toluene and dried for 18 hours and 50°/20 mbar. There were obtained 12.7 g (92%) of (R)-α-(2-pyridyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol; m.p. 130°-131°; 91.8% e.e.; [α]D20 +17.1 ° (c=1, MeOH).

Workup

  1. customA 500 ml autoclave was loaded in a glove box
  2. customwas carried out at 60°, at a constant pressure of 60 bar H2
  3. customAfter a hydrogenation time of 19 hours
  4. customwas 100°
  5. customThe hydrogenation solution was evaporated on a rotary evaporator at 45°/20 mbar
  6. customFor the crystallization of the product
  7. dissolutionthe residue (13.8 g) was dissolved in 21 ml of hot toluene
  8. stirringstirred for 16 hours
  9. customThe crystallization
  10. temperatureby cooling to 1°
  11. stirringstirring for 3 hours
  12. filtrationThe yellow crystals were filtered off
  13. washwashed with cold toluene
  14. customdried for 18 hours and 50°/20 mbar

Sources & evidence

ORD record
ord-1f7d92a5a79e4891b1cc2fa76fb16d51
Source dataset
uspto-grants-1996_04
Patent number
US05508438

Reaction notes

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