Hydrochloric Acid → HCID 59520445, compound

HRID 1162533Notes

Reaction equation

HRID 1162533 reaction equation
C[O:2][C:3](=[O:37])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:12]=2[C:22](=[O:35])[NH:23][CH2:24][CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=2[Cl:34])=[C:7]([Cl:36])[CH:6]=1.[Li+].[OH-].Cl.C(Cl)Cl>C1COCC1.O>[Cl:36][C:7]1[CH:6]=[C:5]([CH2:4][C:3]([OH:37])=[O:2])[CH:10]=[CH:9][C:8]=1[C:11]1[O:15][N:14]=[C:13]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:12]=1[C:22](=[O:35])[NH:23][CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=1[Cl:34]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 6344DichloromethaneHCID 59520400HCID 59520400, compound

Product 1

HCID 59520445HCID 59520445, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The crude (3-Chloro-4-{4-[2-(2,4-dichloro-phenoxy)-ethyl-carbamoyl]-3-phenyl-isoxazol-5-yl}-phenyl)-acetic acid methyl ester 62 is dissolved in THF (2 mL). A solution of 1 M LiOH in H2O (0.6 mL) is added and the mixture is stirred overnight at room temperature. The mixture is acidified with 1 M HCl, DCM (10 mL) is added and the organic layer washed with H2O (3×5 mL). The organic layer is dried (MgSO4), filtered, concentrated and purified on reverse phase HPLC (H2O/MeCN gradient) to afford the title compound J1 as a white solid: 1H-NMR (400 MHz, CDCl3) δ=7.66 (m, 2H), 7.51 (d, J=7.9 Hz, 1H), 7.34-7.19 (m, 6H), 7.09 (dd, J=8.8 Hz, J=2.5 Hz, 1H), 6.62 (d, J=8.8 Hz, 1H), 6.04 (t, J=5.6 Hz, NH), 3.86 (t, J=4.9 Hz, 2H), 3.63 (q, J=5.2 Hz, 2H), 3.51 (s, 2H). MS calculated for C26H20Cl3N2O5 (M+H+) 545.0, found 545.0.

Workup

  1. additionis added
  2. washthe organic layer washed with H2O (3×5 mL)
  3. dry with materialThe organic layer is dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified on reverse phase HPLC (H2O/MeCN gradient)

Sources & evidence

ORD record
ord-00774184fffb4263bd59c0f4a81afe58
Source dataset
uspto-grants-2010_10
Patent number
US07820705B2

Reaction notes

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