Formic Acid → hydroxy [(3S)-3-phenyl-1-({[4-(4-ethynylphenyl)piperazin-1-yl]sulfonyl}methyl)butyl]formamide

HRID 859924Notes

Reaction equation

HRID 859924 reaction equation
[CH:1]([OH:3])=O.C(OC(=O)C)(=O)C.[OH:11][NH:12][CH:13]([CH2:36][C@@H:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH3:38])[CH2:14][S:15]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]#[C:31][Si](C)(C)C)=[CH:26][CH:25]=2)[CH2:20][CH2:19]1)(=[O:17])=[O:16]>C(Cl)Cl>[OH:11][N:12]([CH:13]([CH2:14][S:15]([N:18]1[CH2:19][CH2:20][N:21]([C:24]2[CH:25]=[CH:26][C:27]([C:30]#[CH:31])=[CH:28][CH:29]=2)[CH2:22][CH2:23]1)(=[O:16])=[O:17])[CH2:36][C@@H:37]([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[CH3:38])[CH:1]=[O:3]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 865948461-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}4-[4-(trimethylsilylethynyl)phenyl]piperazine

Product 1

HCID 58765500hydroxy [(3S)-3-phenyl-1-({[4-(4-ethynylphenyl)piperazin-1-yl]sulfonyl}methyl)butyl]formamideYield 15%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To formic acid (3.75 mL, 98 mmol) at 0° C. was added acetic anhydride (750 μL, 7.8 mmol) and the mixture was stirred at 0° C. for 10 minutes. This was added to a solution of 1-{[(4S)-2-(hydroxyamino)-4-phenylpentyl]sulfonyl}-4-[4-(trimethylsilylethynyl)phenyl]piperazine (720 mg, 94 wt %, 1.35 mmol) in CH2Cl2 (5 mL) cooled to 0° C. The reaction was brought quickly to RT and stirred for 20 minutes. Volatiles were then removed in vacuo, and the residue azeotroped with toluene (3×5 mL). The residue was then dissolved in MeOH (10 mL) and heated to 40° C. for two hours. The solution was then cooled to RT and concentrated in vacuo. The residue was then purified by flash chromatography (silica gel, 40–85% EtOAc in iHexane) and evaporated in vacuo. The solid was dissolved in ether/CH2Cl2 and the insoluble contaminant removed by filtration to give the title compound as a pink foam (90 mg, 0.171 mmol, 15%).

Workup

  1. temperaturecooled to 0° C
  2. customwas brought quickly to RT
  3. stirringstirred for 20 minutes
  4. customVolatiles were then removed in vacuo
  5. customthe residue azeotroped with toluene (3×5 mL)
  6. dissolutionThe residue was then dissolved in MeOH (10 mL)
  7. temperatureheated to 40° C. for two hours
  8. temperatureThe solution was then cooled to RT
  9. concentrationconcentrated in vacuo
  10. customThe residue was then purified by flash chromatography (silica gel, 40–85% EtOAc in iHexane)
  11. customevaporated in vacuo
  12. dissolutionThe solid was dissolved in ether/CH2Cl2
  13. customthe insoluble contaminant removed by filtration

Sources & evidence

ORD record
ord-5ba62ed97fbf4c758f8b559ddadac662
Source dataset
uspto-grants-2006_12
Patent number
US07153857B2

Reaction notes

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