m-Chloroperbenzoic acid → HCID 10446064, compound

HRID 1796997Notes

Reaction equation

HRID 1796997 reaction equation
[F:1][CH:2]([F:17])[S:3][C:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][C:9]([F:15])=[CH:10][CH:11]=2)[N:6]([CH3:16])[CH:5]=1.C1C=C(Cl)C=C(C(OO)=[O:26])C=1>C(Cl)Cl>[F:17][CH:2]([F:1])[S:3]([C:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][C:9]([F:15])=[CH:10][CH:11]=2)[N:6]([CH3:16])[CH:5]=1)=[O:26]

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acid2×HCID 22147653HCID 22147653, compound

Product 1

HCID 10446064HCID 10446064, compoundYield 19.4%

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-0e996c4cb8aa468780d16a6bd6355b37
Source dataset
uspto-grants-2006_04
Patent number
US07034040B2

Reaction notes

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