Hydrochloric Acid → 1-Pyrrolidinecarboxylic acid, 4-(acetylthio)-2-(hydroxymethyl)-, 1,1-dimethylethyl ester, (2S,4S)-

HRID 1034522Notes

Reaction equation

HRID 1034522 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11](OS(C)(=O)=O)[CH2:10][C@@H:9]1[CH2:18][OH:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:20]([O-:23])(=[S:22])[CH3:21].[K+].C(OCC)(=O)C.Cl>CN(C)C=O>[C:20]([S:22][C@@H:11]1[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@H:9]([CH2:18][OH:19])[CH2:10]1)(=[O:23])[CH3:21]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 23670855Potassium ethanethioateHCID 50896316Trans-tert-butyl 2-(hydroxymethyl)-4-((methylsulfonyl)oxy)pyrrolidine-1-carboxylate

Product 1

HCID 105165431-Pyrrolidinecarboxylic acid, 4-(acetylthio)-2-(hydroxymethyl)-, 1,1-dimethylethyl ester, (2S,4S)-Yield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (2R,4S)-1-t-butoxycarbonyl-4-methanesulfonyloxypyrrolidine-2-methanol (i.e., a substrate) (11.8 g: 40 mmole) and potassium thioacetate (5.94 g: 52 mmole) in dimethylformamide (120 ml) is stirred at 65° C. for 3.75 hours. The reaction mixture is mixed with ethyl acetate (330 ml), ice water (100 ml), and 1N-hydrochloric acid (20 ml) to adjust the aqueous layer at pH 4. The organic layer is taken, successively washed with water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel chromatography (toluene-ethyl acetate=2:1) to give (2S,4S)-4-acetylthio-1-t-butoxycarbonylpyrrolidine-2-methanol (9.48 g). Yield: 86%. Pale orange colored oil. NMR δ(CDCl3) ppm: 1.47(s, 9H), 2.34(s, 3H), 2.4 to 3.2(m, 2H), 3.58 to 4.1(m, 6H). IR ν (CHCl3) cm-1 : 3380, 1690.

Workup

  1. washsuccessively washed with water and saturated brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by silica gel chromatography (toluene-ethyl acetate=2:1)

Sources & evidence

ORD record
ord-f86e736718e941f8bc12f0f7a9a2303e
Source dataset
uspto-grants-1994_05
Patent number
US05317016

Reaction notes

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