N-methyl-2-pyrrolidone → HCID 86590288, compound

HRID 895346Notes

Reaction equation

HRID 895346 reaction equation
CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:23][O:24][C:25](=[O:58])[CH2:26][N:27]1[CH2:32][CH2:31][N:30]([CH:33]([C:51]2[CH:56]=[CH:55][C:54](Br)=[CH:53][CH:52]=2)[CH2:34][O:35][CH2:36][C:37]2[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[C:39]([C:47]([F:50])([F:49])[F:48])[CH:38]=2)[CH2:29][CH2:28]1.[CH3:59][N:60]1C(=O)CCC1>CC([O-])=O.CC([O-])=O.[Pd+2].[C-]#N.[C-]#N.[Zn+2]>[CH3:23][O:24][C:25](=[O:58])[CH2:26][N:27]1[CH2:32][CH2:31][N:30]([CH:33]([C:51]2[CH:56]=[CH:55][C:54]([C:59]#[N:60])=[CH:53][CH:52]=2)[CH2:34][O:35][CH2:36][C:37]2[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[C:39]([C:47]([F:50])([F:49])[F:48])[CH:38]=2)[CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 80271Tri-o-tolylphosphineHCID 86590287HCID 86590287, compound2×

Product 1

HCID 86590288HCID 86590288, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
50 °C

Procedure

A round-bottomed flask charged with Pd(OAc)2 (36 mg, 4% moles) and P(o-tol)3 (192 mg, 20% mol) was evacuated and then vented to nitrogen. N-methylpyrrolydone (NMP) (4 ml) was added and the mixture was heated at 50° C. for 30 min. Diethylzinc in hexane (0.29 ml) was added and the mixture was maintained at 50° C. for an additional 30 min. The mixture was cannulated into a flask containing a solution of {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-(4-bromo-phenyl)-ethyl]-piperazin-1-yl}-acetic acid methyl ester (compound 184 prepared at example 1.4.1 above; 2.33 g, 4.0 mmoles) and Zn(CN)2 (0.47 g, 4.0 mmoles) dissolved in NMP (6 ml). The reaction mixture was heated at 60° C. for 3 hours. The eluent was evaporated and the residue was taken up in diethylether. The precipitate was filtered and the organic solution was washed with ammonium hydroxyde, dried over MgSO4 and concentrated. The residue was purified by chromatography on silica gel (eluent: Hex/AcOEt: 75/25 v/v) to give {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-(4-cyano-phenyl)-ethyl]-piperazin-1-yl}-acetic acid methyl ester (compound 317; 0.9 g, 34%).

Workup

  1. customwas evacuated
  2. additionN-methylpyrrolydone (NMP) (4 ml) was added
  3. additionDiethylzinc in hexane (0.29 ml) was added
  4. temperaturethe mixture was maintained at 50° C. for an additional 30 min
  5. customThe mixture was cannulated into a flask
  6. temperatureThe reaction mixture was heated at 60° C. for 3 hours
  7. customThe eluent was evaporated
  8. filtrationThe precipitate was filtered
  9. washthe organic solution was washed with ammonium hydroxyde
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography on silica gel (eluent: Hex/AcOEt: 75/25 v/v)

Sources & evidence

ORD record
ord-3655a85dded84e9fb17700e8af09e09b
Source dataset
uspto-grants-2005_07
Patent number
US06916797B2

Reaction notes

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