Methane → HCID 58235363, compound

HRID 1895941Notes

Reaction equation

HRID 1895941 reaction equation
[F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[CH2:17][CH2:16][C@H:15]([O:18][NH2:19])[CH2:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.ClC([O:25][C:26](Cl)(Cl)Cl)=O.C.[F:31][C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=1.C(N(CC)C(C)C)(C)C>O1CCCC1>[F:31][C:32]1[CH:38]=[CH:37][C:35]([NH:36][C:26]([NH:19][O:18][C@H:15]2[CH2:16][CH2:17][N:13]([S:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:20])[F:21])=[CH:9][CH:8]=3)(=[O:11])=[O:12])[CH2:14]2)=[O:25])=[CH:34][CH:33]=1

Participants

7

Reactant 5

HCID 297MethaneHCID 97314-FluoroanilineHCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 67118459HCID 67118459, compound

Product 1

HCID 58235363HCID 58235363, compoundYield 36.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (S)—O-(1-(4-(trifluoromethoxy)phenylsulfonyl)pyrrolidin-3-yl)hydroxylamine (250 mg, 0.76 mmol) in tetrahydrofuran (10 ml) was added over 30 minutes to a suspension of trichloromethyl chloroformate (227 mg, 1.15 mmol) and activated charcoal (20 mg) in tetrahydrofuran (35 ml) at 0° C. over 30 minutes. After stirring at room temperature for 18 hours, the reaction mixture was filtered over silicagel and the filtrate was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (15 ml), 4-fluoroaniline (93.6 mg, 0.84 mmol) and N,N-diisopropylethylamine (296 mg, 2.3 mmol) were added and the whole was stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and the residue was diluted with ethyl acetate (50 ml), washed with H2O (20 ml×2), brine (20 ml×2), dried over Na2SO4 and concentrated in vacuo. The residual solid was recrystallized from diethyl ether to give (S)-1-(4-fluorophenyl)-3-(1-(4-(trifluoromethoxy)phenylsulfonyl)pyrrolidin-3-yloxy)urea as a white solid (127 mg, 36%): LCMS: 464 [M+1]+. 1H NMR (DMSO-d6) δ: 1.85 (m, 1H), 2.09 (m, 1H), 3.25 (m, 3H), 3.53 (d, 1H), 4.36 (s, 1H), 7.07 (t, 2H), 7.47 (d, 2H), 7.56 (d, 2H), 7.92 (d, 2H), 8.63 (s, 1H), 9.45 (s, 1H).

Workup

  1. filtrationthe reaction mixture was filtered over silicagel
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in tetrahydrofuran (15 ml)
  4. stirringthe whole was stirred at room temperature for 18 hours
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. additionthe residue was diluted with ethyl acetate (50 ml)
  7. washwashed with H2O (20 ml×2), brine (20 ml×2)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residual solid was recrystallized from diethyl ether

Sources & evidence

ORD record
ord-f23ffdf55d6a454ca9bf06f9cc50a2f9
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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