Trifluoroacetic acid → HCID 23447406, compound

HRID 1840610Notes

Reaction equation

HRID 1840610 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]2[CH2:20][CH2:19][N:18]([S:21]([C:24]3[CH:29]=[CH:28][C:27]([C:30]#[C:31][Si](C)(C)C)=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH2:17][C:16]2=[O:36])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C1(C)C=CC=CC=1>[C:30]([C:27]1[CH:26]=[CH:25][C:24]([S:21]([N:18]2[CH2:19][CH2:20][N:15]([CH2:14][CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[C:16](=[O:36])[CH2:17]2)(=[O:23])=[O:22])=[CH:29][CH:28]=1)#[CH:31]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69930993HCID 69930993, compound

Product 1

HCID 23447406HCID 23447406, compoundYield 124.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 1-[1-(tert-butoxycarbonyl)-4-(4-iodobenzenesulfonyl)-4-piperidylmethyl]-2-piperazinone (1.13 g), which was produced according to a method described in Reference Example 54 using 1-[1-(tert-butoxycarbonyl)-4-piperidylmethyl]-2-piperazinone and 4-iodobenzenesulfonyl chloride, in diethylamine (20 ml)-DMF (5 ml) were added trimethylsilylacetylene (244 mg), bis(triphenylphosphine)palladium chloride (II) (69 mg) and copper iodide (2 ml), and the mixture was stirred at room temperature for 5 hours. The reaction solution was concentrated, and the residue was purified with silica gel column chromatography (hexane:acetone=1:1) to give brown crystals of 1-[1-(tert-butoxycarbonyl)-4-piperidylmethyl]-4-[4-[2-(trimethylsilyl)ethynyl]benzenesulfonyl]-2-piperazinone (825 mg). To a solution of 1-[1-(tert-butoxycarbonyl)-4-piperidylmethyl]-4-[4-[2-(trimethylsilyl)ethynyl]benzenesulfonyl]-2-piperazinone (534 mg) in toluene (10 ml) was added trifluoroacetic acid (5 ml), and the mixture was stirred for 1 hour. The reaction solution was concentrated, and the residue was dissolved in ethanol (20 ml). To the solution was added 1N sodium hydroxide (2 ml), and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added ethyl acetate, and the mixture was washed with 10% sodium carbonate solution and saturated brine, dried (MgSO4) and concentrated. Precipitated crystals were washed with ethanol-ether to give brown crystals of 4-(4-ethynylbenzenesulfonyl)-1-[4-piperidylmethyl]-2-piperazinone (450 mg). To 10% sodium carbonate solution was added bromopyridine hydrochloride (272 mg), and the mixture was extracted with ethyl acetate, dried and concentrated. To the residue were added 4-(4-ethynylbenzenesulfonyl)-1-[4-piperidylmethyl]-2-piperazinone (289 mg) and isoamylalcohol (10 ml), and the mixture was allowed to react at 130% overnight. The reaction solution was concentrated under reduced pressure, and to the residue was added 10% sodium carbonate solution. The mixture was extracted with ethyl acetate-THF, and the extract was washed with saturated brine, dried and concentrated. The residue was purified with silica gel column chromatography (acetone:methanol=9:1→1:1), washed with water, and precipitated crystals were washed with acetone-ether to give powder of 4-(4-ethynylbenzenesulfonyl)-1-[1-(4-pyridyl)-4-piperidylmethyl]-2-piperazinone (85 mg).

Workup

  1. concentrationThe reaction solution was concentrated
  2. dissolutionthe residue was dissolved in ethanol (20 ml)
  3. additionTo the solution was added 1N sodium hydroxide (2 ml)
  4. stirringthe mixture was stirred at room temperature for 1 hour
  5. additionTo the reaction solution was added ethyl acetate
  6. washthe mixture was washed with 10% sodium carbonate solution and saturated brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customPrecipitated crystals
  10. washwere washed with ethanol-ether

Sources & evidence

ORD record
ord-d51df146266348839687c9333eaceb0f
Source dataset
uspto-grants-2004_01
Patent number
US06680312B2

Reaction notes

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