Potassium Hydroxide → HCID 178480853, compound

HRID 489952Notes

Reaction equation

HRID 489952 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][N:11]=[C:10]([C:13]([N:15]3[CH2:20][CH2:19][N:18]([C:21](OC(C)(C)C)=O)[CH2:17][CH2:16]3)=O)[C:9]=2[C:28]2[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=2)=[CH:4][CH:3]=1.[OH-].[K+].CO.C(OCC)(=O)C.[NH4+].[OH-]>O1CCCC1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:12][N:11]=[C:10]([CH2:13][N:15]3[CH2:16][CH2:17][N:18]([CH3:21])[CH2:19][CH2:20]3)[C:9]=2[C:28]2[CH:29]=[CH:30][N:31]=[CH:32][CH:33]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 14797Potassium HydroxideHCID 21901312Ethyl acetate methanol ammonium hydroxideHCID 178452358HCID 178452358, compound

Product 1

HCID 178480853HCID 178480853, compoundYield 50.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 21226445Aluminium lithium hydrideSolvent2×

Procedure

To a suspension of 1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]carbonyl]-1-piperazinecarboxylate (0.451 g, 1.0 mL) in dry tetrahydrofuran (8 mL), 1.0N LiAlH4 in tetrahydrofuran (2.5 mL, 2.5 mmol) was added dropwise at such a rate as to maintain reflux over 15 minutes. Upon the addition, the suspension became a clear light yellow solution, which was kept boiling for an additional 1.5 hours. Excess LiAlH4 was decomposed by cautious addition of a solution of KOH (0.5611 g, 1.0 mmol) in water (3.5 mL). Upon hydrolysis, a white salt precipitated. After the addition was completed, the mixture was heated to reflux for 1 hour. The hot solution was filtered by suction through a buchner funnel. Any remaining product was extracted from the precipitate by refluxing with tetrahydrofuran (10 mL) for 1 hour, followed again by suction filtration. The combined filtrates were concentrated under reduced pressure to give a crude residue, which was then diluted with ethyl acetate and washed with water and brine. The organic layer was dried over MgSO4. After filtration, the solvent was removed under reduced pressure, and a crude product was obtained. The desired product 1-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]methyl]-4-methylpiperazine (0.1509 g, 50.1%) was obtained by chromatography (silica gel, 70:30:1 methanol/ethyl acetate/NH4OH). Anal. Calc'd for C20H22N5F.0.6H2O: C, 66.32; H, 6.46; N, 19.33; Found: C, 66.31; H, 5.96; N, 18.83. MS (MH+): 352 (base peak).

Workup

  1. additionwas added dropwise at such a rate as
  2. temperatureto maintain
  3. temperaturereflux over 15 minutes
  4. additionUpon the addition
  5. customUpon hydrolysis
  6. customa white salt precipitated
  7. additionAfter the addition
  8. temperaturethe mixture was heated
  9. temperatureto reflux for 1 hour
  10. filtrationThe hot solution was filtered by suction through a buchner funnel
  11. extractionAny remaining product was extracted from the precipitate
  12. temperatureby refluxing with tetrahydrofuran (10 mL) for 1 hour
  13. filtrationfollowed again by suction filtration
  14. concentrationThe combined filtrates were concentrated under reduced pressure
  15. customto give a crude residue, which
  16. washwashed with water and brine
  17. dry with materialThe organic layer was dried over MgSO4
  18. filtrationAfter filtration
  19. customthe solvent was removed under reduced pressure
  20. customa crude product was obtained

Sources & evidence

ORD record
ord-05872518f823409aac6851e3180d7f97
Source dataset
uspto-grants-2005_12
Patent number
US06979686B1

Reaction notes

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