3-Fluoroaniline → HCID 86652733, compound

HRID 1895927Notes

Reaction equation

HRID 1895927 reaction equation
[F:1][C:2]([F:22])([F:21])[O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[CH2:18][CH2:17][CH:16]([O:19][NH2:20])[CH2:15][CH2:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.[C:23](Cl)(=[O:29])OC(Cl)(Cl)Cl.[F:31][C:32]1[CH:33]=[C:34]([CH:36]=[CH:37][CH:38]=1)[NH2:35].C(N(CC)C(C)C)(C)C>O1CCCC1>[F:31][C:32]1[CH:33]=[C:34]([NH:35][C:23]([NH:20][O:19][CH:16]2[CH2:17][CH2:18][N:13]([S:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:21])[F:22])=[CH:9][CH:8]=3)(=[O:11])=[O:12])[CH2:14][CH2:15]2)=[O:29])[CH:36]=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 97423-FluoroanilineHCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 67118448HCID 67118448, compound

Product 1

HCID 86652733HCID 86652733, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of O-(1-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-yl)hydroxylamine (1.02 g, 3.00 mmol) in tetrahydrofuran (20 ml) was added over 1 hour at 0° C. to a solution of trichloromethyl carbonochloridate (890 mg, 4.50 mmol) in tetrahydrofuran (60 ml) and stirred at room temperature for 15 hours. The reaction mixture was concentrated in vacuo and the residue was diluted with tetrahydrofuran (18 ml). 3-Fluoroaniline (100 mg, 0.90 mmol) and N,N-diisopropylethylamine (290 mg, 2.25 mmol) were added and stirred at room temperature for 16 hours. The reaction mixture was quenched with H2O (10 ml) and aqueous 1 N HCl solution (pH=3) and extracted with CH2Cl2 (70 ml×3). The combined organic phase was washed with aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/petroleum ether: 33/67) to give 1-(3-fluorophenyl)-3-(1-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-yloxy)urea (232 mg, 65%) as a white solid: LCMS: 478 [M+1]+. 1H NMR (DMSO-6) δ: 1.78 (m, 2H), 1.92 (m, 2H), 2.85 (m, 2H), 3.22 (m, 2H), 3.78 (m, 1H), 6.79 (m, 1H), 7.28 (m, 2H), 7.46 (m, 1H), 7.63 (m, 2H), 7.89 (m, 2H), 8.75 (s, 1H), 9.51 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionthe residue was diluted with tetrahydrofuran (18 ml)
  3. stirringstirred at room temperature for 16 hours
  4. customThe reaction mixture was quenched with H2O (10 ml) and aqueous 1 N HCl solution (pH=3)
  5. extractionextracted with CH2Cl2 (70 ml×3)
  6. washThe combined organic phase was washed with aqueous NaHCO3 solution and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (ethyl acetate/petroleum ether: 33/67)

Sources & evidence

ORD record
ord-68da76485a6143ddacaf15cb10ec7412
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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