Pyridine → HCID 86671176, compound

HRID 718760Notes

Reaction equation

HRID 718760 reaction equation
[CH2:1]([C:3]12[CH2:18][CH2:17][C:16](=[O:19])[CH:15]=[C:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:9]=12)[CH3:2].N1C=CC=CC=1.[H][H]>C1COCC1.[Pd]>[CH2:1]([C@:3]12[CH2:18][CH2:17][C:16](=[O:19])[CH2:15][C@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:9]=12)[CH3:2].[CH2:1]([C@@:3]12[CH2:18][CH2:17][C:16](=[O:19])[CH2:15][C@@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:9]=12)[CH3:2]

Participants

6

Reactant 3

HCID 1049PyridineHCID 68226904HCID 68226904, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86671176HCID 86671176, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 11b-ethyl-9-hydroxy-1,2,5,6,7,11b-hexahydro-dibenzo[a,c]cyclohepten-3-one (17, R2=Ethyl) (11.25 g, 43.9 mmol) and 10% Pd—C (1.40 g, 1.32 mmol) in THF (80 mL) was added pyridine (20 mL) and the mixture was hydrogenated at rt under about 40 psi of hydrogen for about 18 h. The catalyst was removed by filtration through Celite®, and the filtrate was concentrated. The residue was dissolved in DCM (200 mL) and washed with 2N aq. HCl (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was re-dissolved in EtOAc (100 mL) and DCM (100 mL), filtered through a short pad of silica gel, and concentrated until product began to precipitate. Product was collected by filtration, rinsed with EtOAc (10 mL) and dried under reduced pressure to yield (4aS,11bR)-11b-ethyl-9-hydroxy-1,2,4,4a,5,6,7,11b-octahydro-dibenzo[a,c]cyclohepten-3-one; compound with (4aR,11bS)-11b-ethyl-9-hydroxy-1,2,4,4a,5,6,7,11b-octahydro-dibenzo[a,c]cyclohepten-3-one (18, R2=Ethyl) (6.45 g, 57%) as a white solid. LC/MS, method 1, 0.80 min, 319 (M−H)−. 1H NMR (400 MHz, DMSO) 9.14 (s, 1H), 7.11-7.05 (m, 1H), 6.60-6.54 (m, 2H), 2.96-2.86 (m, 1H), 2.65-2.54 (m, 2H), 2.47-2.36 (m, 1H), 2.29-2.20 (m, 1H), 2.20-2.05 (m, 4H), 1.89-1.79 (m, 1H), 1.71-1.51 (m, 3H), 1.49-1.31 (m, 2H), 0.61 (t, J=7.4 Hz, 3H).

Workup

  1. customThe catalyst was removed by filtration through Celite®
  2. concentrationthe filtrate was concentrated
  3. dissolutionThe residue was dissolved in DCM (200 mL)
  4. washwashed with 2N aq. HCl (100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was re-dissolved in EtOAc (100 mL)
  9. filtrationDCM (100 mL), filtered through a short pad of silica gel
  10. concentrationconcentrated until product
  11. customto precipitate
  12. filtrationProduct was collected by filtration
  13. washrinsed with EtOAc (10 mL)
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-5d381a6021494b46af54b978642f8dbf
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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