Pivaloyl chloride → HCID 10840224, compound

HRID 727690Notes

Reaction equation

HRID 727690 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]([OH:29])=O)[CH2:10]2)=[CH:5][CH:4]=1.C(Cl)(=O)C(C)(C)C.FC(F)(F)C(O)=O.[CH3:46][N:47]([CH3:53])[C@H:48]1[CH2:52][CH2:51][NH:50][CH2:49]1.C(N(C(C)C)CC)(C)C>O1CCCC1.C(#N)C.C(N(CC)CC)C>[CH3:46][N:47]([CH3:53])[C@H:48]1[CH2:52][CH2:51][N:50]([C:27]([C@@H:11]2[CH2:10][C@H:9]([S:8][CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:31][CH:30]=3)[CH2:13][N:12]2[C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=2)=[O:15])=[O:29])[CH2:49]1

Participants

8

Reactant 4

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-prolineHCID 67585128HCID 67585128, compound

Product 1

HCID 10840224HCID 10840224, compoundYield 78.7%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

924 mg of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid were dissolved in 10 ml of dry tetrahydrofuran, and the resulting solution was cooled to -20° C. 209 mg of triethylamine, followed by 250 mg of pivaloyl chloride, were then added to the solution, after which the mixture was stirred at the same temperature for 5 minutes. At the end of this time, a mixture of 651 mg of (3S)-3-dimethylaminopyrrolidine trifluoroacetate, 560 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 1 hour. After this, the reaction mixture was filtered, and the solvent was removed by evaporation under reduced pressure. The resulting residue was diluted with ethyl acetate, and the diluted solution was washed with an aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography, using a 3:1 by volume mixture of acetonitrile and methanol as the eluent, to obtain 884 mg of the title compound as a powder.

Workup

  1. additionwere then added to the solution
  2. additionwas added to the mixture
  3. temperaturethe mixture was gradually heated
  4. stirringstirred at 0° C. for 1 hour
  5. filtrationAfter this, the reaction mixture was filtered
  6. customthe solvent was removed by evaporation under reduced pressure
  7. additionThe resulting residue was diluted with ethyl acetate
  8. washthe diluted solution was washed with an aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  9. dry with materialafter which it was dried over anhydrous magnesium sulfate
  10. customThe solvent was then removed by distillation under reduced pressure
  11. customthe resulting residue was purified by silica gel column chromatography
  12. additionby volume mixture of acetonitrile and methanol as the eluent

Sources & evidence

ORD record
ord-1aca7bfa33b44c988a0035be4d8fe2b1
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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