Hydrochloric Acid → HCID 67055385, compound

HRID 603012Notes

Reaction equation

HRID 603012 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([C@@H:18]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[C:19]3[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=3)[C:22]([OH:24])=[O:23])[CH2:15]2)[C:10]([F:13])([CH3:12])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.Cl.[CH3:36][CH2:37]O>O1CCOCC1>[Br:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([C@@H:18]([C:28]3[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=3)[C:19]3[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=3)[C:22]([O:24][CH2:36][CH3:37])=[O:23])[CH2:15]2)[C:10]([F:13])([CH3:11])[CH3:12])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 67055384HCID 67055384, compound

Product 1

HCID 67055385HCID 67055385, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 5.72 g (10.4 mmol) of 3-[(S)-{3-[(1S)-1-(3-bromo-5-fluorophenyl)-2-fluoro-2-methylpropyl]azetidin-1-yl}(4-chlorophenyl)methyl]benzoic acid in 230 mL of EtOH, was added a solution of 25 mL of 4N HCl in dioxane. After 7.5 h at reflux, the solution was cooled and concentrated to remove solvents. To the residue were added 150 mL of CH2Cl2 and 30 mL of H2O and the pH was adjusted to 7-8 with aq NaHCO3. The aqueous layer was extracted with three 100 mL portions of CH2Cl2 and the combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexanes/ethyl acetate to afford the title compound as a white solid; 1H-NMR(CDCl3) δ 1.25 (d, 3H, J1=22 Hz), 1.27 (d, 3H, J1=22 Hz), 1.40(t, 3H, J=7.1 Hz), 2.34(t, 1H, J=7.5 Hz), 2.83-2.89(m, 2H), 3.10-3.15(m, 2H), 3.62 (m, 1H), 4.30(s, 1H), 4.38 (q, 2H, J1=14.2 Hz, J2=7.1 Hz), 6.85 (d, 1H, J=9.4 Hz), 7.10-7.11(m, 2H), 7.26-7.38 (m, 5H), 7.55 (d, 1H, J=7.8 Hz), 7.86 (d, 1H, J=7.7 Hz), 8.05 (s, 1H); Mass Spectrum: m/e=576, (M+1, 35Cl 79Br), 578 (M+1, 37Cl79Br/35Cl 81Br), 580 (M+1, 37Cl 81Br).

Workup

  1. temperatureAfter 7.5 h at reflux
  2. temperaturethe solution was cooled
  3. concentrationconcentrated
  4. customto remove solvents
  5. additionTo the residue were added 150 mL of CH2Cl2 and 30 mL of H2O
  6. extractionThe aqueous layer was extracted with three 100 mL portions of CH2Cl2
  7. dry with materialthe combined organic layer was dried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-a1c0cef648144f3a9efc968e110cea20
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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