2-Fluoro-5-(trifluoromethyl)phenyl isocyanate → HCID 25106933, compound

HRID 885111Notes

Reaction equation

HRID 885111 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]3([OH:21])[CH2:18][CH2:17][N:16]([CH2:19][CH3:20])[CH2:15][CH2:14]3)=[N:10][CH:9]=2)=[CH:4][C:3]=1[F:22].[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=1[N:34]=[C:35]=[O:36]>O1CCCC1>[CH2:19]([N:16]1[CH2:17][CH2:18][C:13]([C:11]2[S:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:35]([NH:34][C:25]4[CH:26]=[C:27]([C:30]([F:31])([F:33])[F:32])[CH:28]=[CH:29][C:24]=4[F:23])=[O:36])=[C:3]([F:22])[CH:4]=3)=[CH:9][N:10]=2)([OH:21])[CH2:14][CH2:15]1)[CH3:20]

Participants

4

Reactant 2

HCID 27333802-Fluoro-5-(trifluoromethyl)phenyl isocyanateHCID 68720520HCID 68720520, compound

Product 1

HCID 25106933HCID 25106933, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ambient solution of Example 8B (0.02 g, 0.062 mmol) in tetrahydrofuran (1 mL) was added 2-fluoro-5-trifluoromethylphenylisocyanate (0.010 g, 0.065 mmol). After 1 h, the mixture was concentrated under reduced pressure. The residue was purified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography) using a Zorbax SB-C18 7M 21.2×250 mm column with UV detection analyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min). The fractions containing the desired product were diluted with saturated aqueous NaHCO3 and extracted with ethyl acetate. The organic layer was dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.01 (t, J=7.1 Hz, 3H), 1.73 (br d, J=11.9 Hz, 2H), 2.08 (dt, J=11.9 and 3.7 Hz, 2H), 2.25-2.37 (m, 4H), 2.64-2.73 (m, 2H), 6.15 (s, 1H), 7.33-7.52 (m, 3H), 7.61 (m, 1H), 8.05 (s, 1H), 8.24 (m, 1H), 8.64 (m, 1H), 8.90 (s, 1H), 9.34 (s, 1H); MS (ESI) m/z 527 [M+H]+.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customThe residue was purified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography)
  3. customanalyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min)
  4. additionThe fractions containing the desired product
  5. additionwere diluted with saturated aqueous NaHCO3
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried with anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-640c243e29c6466bb5d92b1956640233
Source dataset
uspto-grants-2012_08
Patent number
US08242139B2

Reaction notes

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