1-Methylpiperazine → 3-Methoxy-4-[(trimethylsilyl)ethynyl]phenyl-4-methylpiperazine

HRID 1403208Notes

Reaction equation

HRID 1403208 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][Si:10]([CH3:13])([CH3:12])[CH3:11])=[C:4]([O:14][CH3:15])[CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:26][N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2(N(C)C)CC=CC=C2C2C=CC=CC=2)CCCCC1>[CH3:15][O:14][C:4]1[CH:3]=[C:2]([N:30]2[CH2:31][CH2:32][N:27]([CH3:26])[CH2:28][CH2:29]2)[CH:7]=[CH:6][C:5]=1[C:8]#[C:9][Si:10]([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 3

HCID 531671-MethylpiperazineHCID 2733832Lithium HexamethyldisilazideHCID 71239496[(4-Bromo-2-methoxyphenyl)ethynyl](trimethyl)silane

Product 1

HCID 867252923-Methoxy-4-[(trimethylsilyl)ethynyl]phenyl-4-methylpiperazineYield 68.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 665453382-Dicyclohexylphosphino-2-(N,N-Dimethylamino)BiphenylCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of [(4-bromo-2-methoxyphenyl)ethynyl](trimethyl)silane (1.426 g, 5.035 mmol) in dry THF (25 mL) was degassed and backfilled with argon for three times. Pd2(dba)3 (230.5 mg, 0.252 mmol) and 2-dicyclohexylphosphino-2-(N,N′-dimethylamino)biphenyl (79.3 mg, 0.201 mmol) were added under argon atmosphere and the mixture was degassed and backfilled with argon for three times. Then 1 M LiHMDS in THF (12.1 mL, 12.084 mmol) and N-methylpiperazine (1.34 mL, 1.21 g, 12.083 mmol) were added by a syringe and the mixture was degassed and backfilled with Argon for three times. The reaction mixture was heated to reflux for 1 h. After cooling to room temperature the reaction mixture was filtered on a pad of celite washing with THF (200 mL). The filtrate was evaporated under vacuum and the black oil so obtained was purified by chromatography on silica gel (DCM/MeOH 9/1) to afford the title compound as a brownish solid (1.042 g, 68.4%).

Workup

  1. customthe mixture was degassed
  2. customthe mixture was degassed
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 1 h
  5. filtrationwas filtered on a pad of celite
  6. washwashing with THF (200 mL)
  7. customThe filtrate was evaporated under vacuum
  8. customthe black oil so obtained
  9. customwas purified by chromatography on silica gel (DCM/MeOH 9/1)

Sources & evidence

ORD record
ord-2647c7aa74384512ad91b54f599d80a0
Source dataset
uspto-grants-2014_12
Patent number
US08912200B2

Reaction notes

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