Ethyl Acetate → HCID 22843101, compound

HRID 2372711Notes

Reaction equation

HRID 2372711 reaction equation
[CH2:1]([O:8][C:9]([C@H:11]1[NH:15][C:14](=[O:16])[C@H:13](OS(C)(=O)=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][SH:29])=[CH:26][CH:25]=1.C1CCN2C(=NCCC2)CC1.C(OCC)(=O)C>CN(C=O)C>[CH2:1]([O:8][C:9]([C@H:11]1[NH:15][C:14](=[O:16])[CH:13]([S:29][CH2:28][C:27]2[CH:30]=[CH:31][C:24]([O:23][CH3:22])=[CH:25][CH:26]=2)[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 804074-Methoxy-alpha-toluenethiolHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 54076256HCID 54076256, compound

Product 1

HCID 22843101HCID 22843101, compoundYield 111.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

16.3 g (52.1 mmol) of (3R,5S)-5-benzyloxycarbonyl-3-mesyloxypyrrolidin-2-one was dissolved in 82 ml of DMF, and 7.95 ml (57.3 mmol) of p-methoxybenzylmercaptan was added to the solution under cooling with ice, then 8.48 ml (56.7 mmol) of DBU was added dropwise thereto. The mixture was stirred for 15 minutes at room temperature. Ethyl acetate was added to the reaction mixture, which was washed sequentially with water, 1 N HCl, a saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution. The ethyl acetate solution was dried over anhydrous magnesium sulfate and the solvent was distilled off to obtain 21.6 g of (3RS,5S)-5-benzyloxycarbonyl-3-p-methoxybenzylthiopyrrolidin-2-one as an oily substance. This oily substance was dissolved in 122 ml of methanol, and 36.5 ml of 2N NaOH was added thereto under cooling with ice, and then the mixture was stirred for 1 hour at the same temperature. After the reaction mixture was washed twice with ethyl acetate, the aqueous layer was adjusted to pH 2.0 with 2N HCl, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was triturated with isopropyl ether to obtain 10.6 g of (3RS,5S)-3-p-methoxybenzylthio-2-oxopyrrolidin-5-carboxylic acid. This was dissolved in 348 ml of THF, and 6.17 g (75.7 mmol) of dimethylamine hydrochloride and 11.5 g (94.3 mmol) of 4-dimethylaminopyridine were added thereto under cooling with ice. And then, a solution of 11.7 g (56.8 mmol) of DCC in 37 ml of THF was added dropwise thereto. The mixture was stirred for 3 hours at the same temperature, and then for 1 day at room temperature. After the precipitate was filtered off, ethyl acetate was added to the filtrate, which was washed with lN HCl. The solution was dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (Wakogel® C-300, elution with 1-2% methanol-chloroform) to obtain 5.33 g (yield: 28.4%) of (3S,5S)-5-dimethylcarbamoyl-3-p-methoxybenzylthiopyrrolidin-2-one as an oil and 4.41 g (yield: 23.5%) of (3R,5S)-5-dimethylcarbamoyl-3-p-methoxybenzylthiopyrrolidin-2-one as a powder.

Workup

  1. temperatureunder cooling with ice
  2. washwas washed sequentially with water, 1 N HCl
  3. dry with materialThe ethyl acetate solution was dried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-5fb896d792f542358a4eeb5d360283be
Source dataset
uspto-grants-1992_03
Patent number
US05100888

Reaction notes

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