Pivaloyl chloride → HCID 67881956, compound

HRID 727692Notes

Reaction equation

HRID 727692 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 67612276HCID 67612276, compound

Product 1

HCID 67881956HCID 67881956, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

2.60 g of (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid were dissolved in 20 ml of dry tetrahydrofuran, and the resulting solution was cooled to -20° C. 590 mg of triethylamine and then 704 mg of pivaloyl chloride were added to the solution, after which the resulting mixture was stirred at the same temperature for 5 minutes. 2100 g of (3R)-3-dimethylaminopyrrolidine trifluoroacetate, 788 mg of diisopropylethylamine and 20 ml of dry acetonitrile were then added, in that order, to the mixture, and the mixture was gradually heated and then stirred at 0° C. for 1 hour. The reaction mixture was then filtered, and the solvent was removed by evaporation under reduced pressure. The 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. It was then dried over anhydrous magnesium sulfate. The solvent was 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 2.56 g of the title compound as a powder.

Workup

  1. temperaturethe mixture was gradually heated
  2. stirringstirred at 0° C. for 1 hour
  3. filtrationThe reaction mixture was then filtered
  4. customthe solvent was removed by evaporation under reduced pressure
  5. additionThe residue was diluted with ethyl acetate
  6. washthe 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 materialIt was then dried over anhydrous magnesium sulfate
  8. customThe solvent was removed by distillation under reduced pressure
  9. customthe resulting residue was purified by silica gel column chromatography
  10. additionby volume mixture of acetonitrile and methanol as the eluent

Sources & evidence

ORD record
ord-2d2c996f93374722b07b477ebdf2ae63
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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