Triethylamine → 4-((4-Chlorophenyl)sulfonyl)-5,8-difluoro-2H-chromene

HRID 1047495Notes

Reaction equation

HRID 1047495 reaction equation
ClC1C=CC(S[CH:9]2[C:18]3[C:13](=[C:14]([F:20])[CH:15]=[CH:16][C:17]=3[F:19])[O:12][CH2:11][CH:10]2O)=CC=1.[CH:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24](C(OO)=O)[CH:23]=1.[O-:33][S:34]([O-:37])(=S)=O.[Na+].[Na+].S(Cl)(C)(=O)=O.C(N(CC)CC)C>C(Cl)Cl.O>[Cl:28][C:26]1[CH:27]=[CH:22][C:23]([S:34]([C:9]2[C:18]3[C:13](=[C:14]([F:20])[CH:15]=[CH:16][C:17]=3[F:19])[O:12][CH2:11][CH:10]=2)(=[O:37])=[O:33])=[CH:24][CH:25]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 24477Sodium ThiosulfateHCID 31297Methanesulfonyl chlorideHCID 70297m-Chloroperbenzoic acidHCID 584453284-((4-Chlorophenyl)thio)-5,8-difluorochroman-3-ol

Product 1

HCID 582522424-((4-Chlorophenyl)sulfonyl)-5,8-difluoro-2H-chromeneYield 38.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

4-(4-Chloro-phenylsulfanyl)-5,8-difluoro-chroman-3-ol (23.2, 71 mmole) was dissolved in 200 ml DCM and MCPBA (77%, 31.7 g, 142 mmole) was added. The reaction was stirred at room temperature for 3 hours. 10 g Na2S2O3 in 50 ml water was added to quench the reaction. The organic layer was washed with 1N NaOH solution (2×100 ml), brine (100 ml), dried over Na2SO4 and concentrated. The residue was dissolved in 200 ml DCM, mesyl chloride (16.1 g, 142 mmole) and triethylamine (14.3 g, 142 mmole) were added. The reaction was stirred at room temperature for one hour. The reaction solution was washed with brine (100 ml), dried over Na2SO4 and concentrated. The residue was recrystallized from EtOAc/Hexane solution to give rise to 8.4 g pure product. The residue from mother liquor was purified by column chromatography (EtOAc/hexane from 0/100 to 25/75 in 55 minute, 7.1 g). Total yield: 15.5 g, 64%. 1H NMR (CDCl3 400 MHz δ 7.84 (dd, J=8.8 and 2.2 Hz, 2H), 7.51 (d, J=8.1 Hz, 2H), 7.30 (t, J=4.4 Hz, 1H), 7.00 (m, 1H), 6.54 (m, 1H), 4.99 (d, J=4.4 Hz, 2H).

Workup

  1. customto quench
  2. customthe reaction
  3. washThe organic layer was washed with 1N NaOH solution (2×100 ml), brine (100 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in 200 ml DCM
  7. stirringThe reaction was stirred at room temperature for one hour
  8. washThe reaction solution was washed with brine (100 ml)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe residue was recrystallized from EtOAc/Hexane solution

Sources & evidence

ORD record
ord-6f10d69d2b4342be8898f9d4828543dd
Source dataset
uspto-grants-2013_10
Patent number
US08569521B2

Reaction notes

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