Isatin → 3-[(Methylsulfonyl)amino]-2-phenylquinoline-4-carboxylic acid

HRID 655907Notes

Reaction equation

HRID 655907 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=[O:3].[OH-:12].[Na+].O=[C:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:16][NH:17][S:18]([CH3:21])(=[O:20])=[O:19]>O.C(O)C.C1COCC1.O>[CH3:21][S:18]([NH:17][C:16]1[C:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:1][C:11]2[C:6]([C:4]=1[C:2]([OH:12])=[O:3])=[CH:7][CH:8]=[CH:9][CH:10]=2)(=[O:20])=[O:19]

Participants

6

Reactant 3

HCID 7054IsatinHCID 14798Sodium HydroxideHCID 21893541N-(2-oxo-2-phenylethyl)methanesulfonamide

Product 1

HCID 578935713-[(Methylsulfonyl)amino]-2-phenylquinoline-4-carboxylic acidYield 70.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 18504229Ethanol tetrahydrofuran waterSolvent

Procedure

To isatin (441 mg, 3 mmol) was added a solution of sodium hydroxide (1.15 g, 29.0 mmol) in water (2.5 mL). The resulting brown precipitate was stirred vigorously at RT for 20 minutes before being heated to 85° C. A solution of N-(2-oxo-2-phenylethyl)methanesulfonamide (1b) (639 mg, 3.0 mmol) in ethanol/THF/water (6.3 mL/1.25 mL/6.3 mL was then added dropwise over 30 minutes. The reaction mixture was stirred at 85° C. for further 4 h before cooling to RT. All organic solvents were removed in vacuo and the aqueous residue reduced to a volume of approximately 6 mL. The aqueous residue was washed with ether (3×10 mL) and then the aqueous residue were acidified with cooling to pH 4 with acetic acid. The precipitate formed were collected, washed with water and dried to give the title compound as a solid (721 mg, 70.3%). 1H NMR (300 MHz, CDCl3) δ 3.11 (s, 3H), 7.05 (d, 1H), 7.39 (d, 2H), 7.64 (m, 2H), 7.78 (m, 1H), 8.06 (m, 1H), 8.19 (m, 1H), 8.47 (m, 1H), 10.03 (b, 2H). MS APCI, m/z=343 (M+1). LCMS: 1.07 min.

Workup

  1. temperaturebefore being heated to 85° C
  2. stirringThe reaction mixture was stirred at 85° C. for further 4 h
  3. temperaturebefore cooling to RT
  4. customAll organic solvents were removed in vacuo
  5. washThe aqueous residue was washed with ether (3×10 mL)
  6. temperaturewith cooling to pH 4 with acetic acid
  7. customThe precipitate formed
  8. customwere collected
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-165d3cf085a645878b5d29529323d7ab
Source dataset
uspto-grants-2011_12
Patent number
US08071621B2

Reaction notes

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