m-Chloroperbenzoic acid → 3-Carboxymethylsulfinyl-7-fluoro-1-methyl-4-quinolone

HRID 1823819Notes

Reaction equation

HRID 1823819 reaction equation
[C:1]([CH2:4][S:5][C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([F:17])=[CH:12][CH:13]=2)[N:8]([CH3:18])[CH:7]=1)([OH:3])=[O:2].C1C=C(Cl)C=C(C(OO)=[O:27])C=1>C(Cl)Cl>[C:1]([CH2:4][S:5]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][C:11]([F:17])=[CH:12][CH:13]=2)[N:8]([CH3:18])[CH:7]=1)=[O:27])([OH:3])=[O:2]

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acid2×HCID 11161467HCID 11161467, compound

Product 1

HCID 101254203-Carboxymethylsulfinyl-7-fluoro-1-methyl-4-quinoloneYield 18.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution (a part remained undissolved) of crude 3-difluoromethylthio-7-fluoro-1-methyl-4-quinolone (4) (3.43 g, 13.23 mmol) in DCM (200 ml) at 0° C. was added ˜80% MCPBA (2.50 g, 11.59 mmol) in a few portions over a period of approximately 1 min. The stirred mixture was allowed to warm to room temperature and was stirred for 30 min. An additional amount of MCPBA (640 mg) was added in 5 portions in approximately 1 h intervals, and the progress of the oxidation was monitored by 1H NMR 30 min after each addition. The mixture was washed with 5% aqueous Na2CO3 (70 ml), the aqueous layer was extracted with DCM (2×200 ml), the combined extracts were dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on silica gel with DCM and then with hexane-ethyl acetate (gradient 2:1,1:1,1:2) to give 980 mg (20.7%; two steps) of the product. The product was further purified by recrystallization from absolute ethanol to give 620 mg (13.1%) of 3-difluoromethylsulfinyl-7-fluoro-1-methyl-4-quinolone (5) as off-white crystals. 1H NMR, CDCl3; δ=3.94 s, 3H, N—CH3; 7.050, 6.870, 6.866, 6.686 (4 lines, X part of ABX), 1H, CHF2; 7.21 dd, 1H, J=10.2 & 2.4 Hz, H at C8, 7.27 ddd, 1H, J=8.9, 7.9 & 2.2 Hz, H at C6; 7.99 s, 1H, H at C2; 8.44 dd, 1H, J=9.0 & 6.3 Hz, H at C5.

Workup

  1. customat 0° C.
  2. additionafter each addition
  3. washThe mixture was washed with 5% aqueous Na2CO3 (70 ml)
  4. extractionthe aqueous layer was extracted with DCM (2×200 ml)
  5. dry with materialthe combined extracts were dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel with DCM
  8. customwith hexane-ethyl acetate (gradient 2:1,1:1,1:2) to give 980 mg (20.7%; two steps) of the product
  9. customThe product was further purified by recrystallization from absolute ethanol

Sources & evidence

ORD record
ord-e5ff98ee37ef46b6800cb9091bf43cc7
Source dataset
uspto-grants-2006_05
Patent number
US07041677B2

Reaction notes

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