Hydrochloric Acid → Ethyl 3-{1-[1-(diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorobenzoate

HRID 602985Notes

Reaction equation

HRID 602985 reaction equation
[C:1]1([CH:7]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:8]2[CH2:11][CH:10]([CH:12]([C:17]3[CH:18]=[C:19]([CH:23]=[C:24]([F:26])[CH:25]=3)[C:20]([OH:22])=[O:21])[C:13]([F:16])([CH3:15])[CH3:14])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:34][CH2:35]O>O1CCOCC1>[C:27]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[CH2:9][CH:10]([CH:12]([C:17]3[CH:18]=[C:19]([CH:23]=[C:24]([F:26])[CH:25]=3)[C:20]([O:22][CH2:34][CH3:35])=[O:21])[C:13]([F:16])([CH3:15])[CH3:14])[CH2:11]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 670553813-{1-[1-(Diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorobenzoic acid

Product 1

HCID 67055389Ethyl 3-{1-[1-(diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 7.5 g (17.15 mmol) of 3-{1-[1-(diphenylmethyl)azetidin-3-yl]-2-fluoro-2-methylpropyl}-5-fluorobenzoic acid, 25 mL of 4N HCl in dioxane, and 200 mL of EtOH was refluxed. After 10 h, it was concentrated to remove solvents. To the residue was added 150 mL of CH2Cl2 and 30 mL of H2O and pH was adjusted to 7-8 with aq NaHCO3, then extracted with CH2Cl2. 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 an white solid; 1H-NMR(CDCl3) δ 1.25(d, 3H, J=22 Hz), 1.30(d, 3H, J=22 Hz), 1.42 (t, 3H, J=7.1 Hz), 2.35 (t, 1H, J=8 Hz), 2.89 (t, 1H, J=8 Hz), 2.97 (m, 1H), 3.12 (m, 1H), 3.24 (m, 1H), 3.68 (t, 1H, J=6 Hz), 4.27 (s, 1H), 4.38 (q, 2H, J1=14, J2=7 Hz), 7.103-7.66 (m, 13H); Mass Spectrum: m/e=464 (M+1).

Workup

  1. temperaturewas refluxed
  2. concentrationit was concentrated
  3. customto remove solvents
  4. additionTo the residue was added 150 mL of CH2Cl2 and 30 mL of H2O and pH
  5. extractionextracted with CH2Cl2
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-4d8a3dd691884de99a86d5a34ab073c4
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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