Chlorosulfonic acid → 4-((S)-3-(6-Chloro-3,4-dihydroquinolin-1(2H)-yl)-2-oxopyrrolidin-1-yl)-benzene-1-sulfonyl chloride

HRID 1696160Notes

Reaction equation

HRID 1696160 reaction equation
[Cl:1][S:2]([OH:5])(=O)=[O:3].[Cl:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]([C@H:17]1[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:18]1=[O:28])[CH2:12][CH2:11][CH2:10]2>CCOC(C)=O>[Cl:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]([C@H:17]1[CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[CH:24][C:25]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:26][CH:27]=3)[C:18]1=[O:28])[CH2:12][CH2:11][CH2:10]2

Participants

4

Reactant 2

HCID 24638Chlorosulfonic acidHCID 58215259(S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-phenylpyrrolidin-2-one

Product 1

HCID 582150924-((S)-3-(6-Chloro-3,4-dihydroquinolin-1(2H)-yl)-2-oxopyrrolidin-1-yl)-benzene-1-sulfonyl chlorideYield 61%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Prepared using general procedure 62: To chlorosulfonic acid (15 mL, 220 mmol) at 0° C. under N2 was added (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-phenylpyrrolidin-2-one (2.43 g, 7.4 mmol) in portions. The reaction mixture was heated to 50° C. for 15 min. and, after cooling to RT, carefully poured onto ice-water (500 mL). EtOAc (150 mL) was added, the phases were separated, and the aqueous layer was extracted with EtOAc (2×150 mL). The combined organic extracts were dried over MgSO4 and concentrated. Purification via silica gel chromatography using 50-80% EtOAc in hexane gave 4-((S)-3-(6-Chloro-3,4-dihydroquinolin-1(2H)-yl)-2-oxopyrrolidin-1-yl)-benzene-1-sulfonyl chloride as an off-white solid (1.92 g, 61%). 1H NMR (400 MHz, DMSO-d6) δ 7.66 (dd, J=2.1, 6.8 Hz, 2H), 7.61 (dd, J=2.1, 6.8 Hz, 2H), 6.99 (d, J=9.0 Hz, 2H), 6.77 (d, J=8.7 Hz, 1H), 5.01-4.96 (m, 1H), 3.85-3.81 (m, 2H), 3.17 (t, J=5.6 Hz, 2H), 2.70 (t, J=6.4 Hz, 2H), 2.42-2.32 (m, 1H), 2.15-2.08 (m, 1H), 1.92-1.79 (m, 2H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=425.1; tR=4.03 min

Workup

  1. customPrepared
  2. temperatureafter cooling to RT
  3. additioncarefully poured onto ice-water (500 mL)
  4. customthe phases were separated
  5. extractionthe aqueous layer was extracted with EtOAc (2×150 mL)
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. concentrationconcentrated
  8. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-840412ac51a644f593ec928ddd43b93e
Source dataset
uspto-grants-2012_04
Patent number
US08163720B2

Reaction notes

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