Water → 3-Pyrrolidinol, 1-[(4-methylphenyl)sulfonyl]-, 3-(4-methylbenzenesulfonate), (3S)-

HRID 2118059Notes

Reaction equation

[NH:1]1[CH2:5][CH2:4][C@H:3]([OH:6])[CH2:2]1.[C:7]1([CH3:17])[CH:12]=[CH:11][C:10]([S:13](Cl)(=[O:15])=[O:14])=[CH:9][CH:8]=1.[OH-:18].[Na+].[OH2:20]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[S:13]([N:1]1[CH2:5][CH2:4][C@H:3]([O:6][S:13]([C:10]2[CH:11]=[CH:12][C:7]([CH3:17])=[CH:8][CH:9]=2)(=[O:20])=[O:18])[CH2:2]1)([C:10]1[CH:11]=[CH:12][C:7]([CH3:17])=[CH:8][CH:9]=1)(=[O:15])=[O:14]

Participants

Conditions

Temperature: 57.5 °C

Procedure

(S)-3-pyrrolidinol (30 g, 0.344 moles) was dissolved in toluene (150 ml) and tetrabutylammonium bromide (3.39 g, 0.0105 moles) was added to the solution. p-Toluensulfonylchloride (140.94 g, 0.7393 moles) was then added portion-wise to the solution, causing the temperature of the solution to rise to 35 to 40° C. Then, 30% NaOH (112.1 g, 0.8407 moles) was slowly added to the solution over about 1 hour, causing the temperature of the solution to rise to 55 to 60° C. After maintaining the solution for 5 hours at 55-60° C., the reaction was complete. Water (30 ml) was then added, and the resulting suspension was cooled to 0° C. over 1 hour to give a solid. The solid was filtered and washed with cold toluene and water to give the title compound. (Dry weight 127.95 g, yield 94%, HPLC purity 99.2% area). The main impurity is 1-tosyl-3-(S)-pyrrolidinol (reaction intermediate) in an amount of 0.05% area by HPLC.

Workup

customto rise to 35 to 40° C
customto rise to 55 to 60° C
temperaturethe resulting suspension was cooled to 0° C. over 1 hour
customto give a solid
filtrationThe solid was filtered
washwashed with cold toluene and water

Sources & evidence

ORD record: ord-1098bb4f5d614ba98612f4b800ed5080
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07442806B2

Reaction notes

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