Pivaloyl chloride → HCID 67585187, compound

HRID 727728Notes

Reaction equation

HRID 727728 reaction equation
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)=[O:15])[C@H:11]([C:27](O)=[O:28])[CH2:10]2)=[CH:5][CH:4]=1.C(Cl)(=O)C(C)(C)C.FC(F)(F)C(O)=O.[N:46]1([C@H:51]2[CH2:55][CH2:54][NH:53][CH2:52]2)[CH:50]=[N:49][CH:48]=[N:47]1.C(N(C(C)C)CC)(C)C>O1CCCC1.C(#N)C.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:19]=[CH:20][C:21]([N+:24]([O-:26])=[O:25])=[CH:22][CH:23]=3)=[O:15])[C@H:11]([C:27]([N:53]3[CH2:54][CH2:55][C@H:51]([N:46]4[CH:50]=[N:49][CH:48]=[N:47]4)[CH2:52]3)=[O:28])[CH2:10]2)=[CH:30][CH:31]=1

Participants

8

Reactant 4

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-prolineHCID 22881680HCID 22881680, compound

Product 1

HCID 67585187HCID 67585187, compoundYield 150.2%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

768 mg of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid were dissolved in 8 ml of dry tetrahydrofuran, and the resulting solution was cooled to 0° C. 191 mg of triethylamine were added to the solution, followed by 218 mg of pivaloyl chloride, and then the mixture was stirred at the same temperature for 5 minutes. At the end of this time, a mixture of 238 mg of (3S)-3-(1-1,2,4-triazolyl)pyrrolidine trifluoroacetate, 440 mg of diisopropylethylamine and 7 ml of dry acetonitrile was added to the mixture, and the mixture was gradually heated and then stirred at 0° C. for 15 minutes and at room temperature for 2 hours. The solvent was then removed by evaporation under reduced pressure, and the residue was diluted with ethyl acetate, after which the diluted solution was washed with an aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order, and dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography, using a 7:1 by volume mixture of ethyl acetate and methanol as the eluent, to give 803 mg of the title compound, as a powder.

Workup

  1. additionwas added to the mixture
  2. temperaturethe mixture was gradually heated
  3. stirringstirred at 0° C. for 15 minutes and at room temperature for 2 hours
  4. customThe solvent was then removed by evaporation under reduced pressure
  5. additionthe residue was diluted with ethyl acetate
  6. washafter which the diluted solution was washed with an aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was then removed by distillation under reduced pressure
  9. customthe residue was purified by silica gel column chromatography
  10. additionby volume mixture of ethyl acetate and methanol as the eluent

Sources & evidence

ORD record
ord-d699482bc5184233871837c8b022bd2b
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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