Trifluoroacetic acid → HCID 69689539, compound

HRID 343079Notes

Reaction equation

HRID 343079 reaction equation
[NH2:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=NO)[CH3:12])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C([N:17](CC)CC)C.C([N-][CH:26]([CH3:28])[CH3:27])(C)C.[Li+].[F:30][CH:31]([F:37])[C:32]([O:34]CC)=O.FC(F)(F)C(O)=O.O1[CH2:49][CH2:48][CH2:47][CH2:46]1>O>[F:37][CH:31]([F:30])[C:32]1[O:34][N:17]=[C:12]([C:48]2[CH:49]=[CH:28][C:26]([CH3:27])=[CH:46][CH:47]=2)[C:11]=1[C:8]1[CH:7]=[CH:6][C:5]([S:2]([NH2:1])(=[O:3])=[O:4])=[CH:10][CH:9]=1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 9961Ethyl difluoroacetateHCID 2724682Lithium diisopropylamideHCID 86753581HCID 86753581, compound

Product 1

HCID 69689539HCID 69689539, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-78 °C

Procedure

1-(4-Methylphenyl)-2-(4-aminosulfonylphenyl-ethan-1-one oxime from Step 3 (2.0 g, 6.6 mmol), tetrahydrofuran (100 mL), and triethylamine (0.67 g, 6.6 mmol) were stirred at room temperature and treated with bis(1,2-chlorodimethylsilyl)ethane (1.42 g, 6.6 mmol). The solution was cooled to -78° C. under nitrogen. Lithium diisopropylamide (2.0M solution in heptane/tetrahydrofuran/ethylbenzene, 10.9 mL, 21.8 mmol) was added dropwise, and the cooling bath was removed. When the temperature reached -15° C., ethyl difluoroacetate (0.82 g, 6.6 mmol) was added all at once. After stirring for 0.5 hour, trifluoroacetic acid (30 mL) and water (10 mL) were added. The resulting dark mixture was heated to reflux for 20 hours, concentrated, dissolved in ethyl acetate (100 mL), washed with brine, saturated aqueous NaHCO3, and water, dried over MgSO4, and concentrated. A dark oily solid was purified by flash column chromatography eluting with ethyl acetate:hexane (1:1). The appropriate fractions were concentrated and crystallized from ethyl acetate/hexane to yield a white solid (0.23 g, 10%): mp 169.0°-172.3° C. 1H NMR (acetone-d6 /300 MHz) 8.0 (d, J=8.4 Hz, 2H), 7.5 (d, J=8.1 Hz, 2H), 7.3 (d, J=8.1 Hz, 2H), 7.2 (d, J=8.1 Hz, 2H), 7.1 (t, J=51.9 Hz, 1H), 6.7 (bs, 2H), 2.4 (s, 3H). High resolution mass spectrum calc'd. for C17H15F2N2O3S(M+H): 365.0771. Found: 365.0779.

Workup

  1. customthe cooling bath was removed
  2. customreached -15° C.
  3. temperatureThe resulting dark mixture was heated
  4. temperatureto reflux for 20 hours
  5. concentrationconcentrated
  6. dissolutiondissolved in ethyl acetate (100 mL)
  7. washwashed with brine, saturated aqueous NaHCO3, and water
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customA dark oily solid was purified by flash column chromatography
  11. washeluting with ethyl acetate:hexane (1:1)
  12. concentrationThe appropriate fractions were concentrated
  13. customcrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-06be4e61b2884320a66b8943bb5c8a9f
Source dataset
uspto-grants-1999_01
Patent number
US05859257

Reaction notes

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