Chlorosulfonic acid → 4-((S)-3-(4-chloro-5-fluoroindolin-1-yl)-2-oxopyrrolidin-1-yl)benzene-1-sulfonyl chloride

HRID 2043196Notes

Reaction equation

[Cl:1][S:2]([OH:5])(=O)=[O:3].[Cl:6][C:7]1[C:15]([F:16])=[CH:14][CH:13]=[C:12]2[C:8]=1[CH2:9][CH2:10][N:11]2[C@H:17]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:18]1=[O:28]>CCOC(C)=O>[Cl:6][C:7]1[C:15]([F:16])=[CH:14][CH:13]=[C:12]2[C:8]=1[CH2:9][CH2:10][N:11]2[C@H:17]1[CH2:21][CH2:20][N:19]([C:22]2[CH:23]=[CH:24][C:25]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:26][CH:27]=2)[C:18]1=[O:28]

Participants

Conditions

Temperature: 60 °C

Procedure

Prepared using general procedure 62: To chlorosulfonic acid (2.0 mL) at 0° C. under N2 was added (S)-3-(4-chloro-5-fluoroindolin-1-yl)-1-phenylpyrrolidin-2-one (1.92 g, 5.8 mmol) in portions. The reaction mixture was heated to 60° C. for 20 min. and, after cooling to RT, carefully poured onto ice-water. EtOAc was added, the phases were separated, and the aqueous layer was extracted with EtOAc (2×). The combined organic extracts were dried over MgSO4 and concentrated to give 4-((S)-3-(4-chloro-5-fluoroindolin-1-yl)-2-oxopyrrolidin-1-yl)benzene-1-sulfonyl chloride which was used without further purification. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=429.3; tR=2.14 min.

Workup

customPrepared
temperatureafter cooling to RT
additioncarefully poured onto ice-water
customthe phases were separated
extractionthe aqueous layer was extracted with EtOAc (2×)
dry with materialThe combined organic extracts were dried over MgSO4
concentrationconcentrated

Sources & evidence

ORD record: ord-bfcb1ab192bc45b99e103b541f4ff778
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586589B2

Reaction notes

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