Lithium Hydroxide → HCID 9549255, compound

HRID 1162526Notes

Reaction equation

HRID 1162526 reaction equation
C[O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[C:15]([C:16](=[O:29])[NH:17][CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=3[Cl:28])=[C:14]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[O:13][N:12]=2)[CH:6]=1.[Li+].[OH-]>COCCOC.O>[Cl:28][C:22]1[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:21]=1[O:20][CH2:19][CH2:18][NH:17][C:16]([C:15]1[C:11]([C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([CH2:4][C:3]([OH:36])=[O:2])[CH:6]=2)=[N:12][O:13][C:14]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:29]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 68648367HCID 68648367, compound

Product 1

HCID 9549255HCID 9549255, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

The crude (3-{4-[2-(2,4-dichloro-phenoxy)-ethyl-carbamoyl]-5-phenyl-isoxazol-3-yl}-phenyl)-acetic acid methyl ester 51 is dissolved in DME (2 mL). A solution of 1 M LiOH in H2O (0.2 mL) and is added and the mixture is stirred overnight at room temperature. The mixture is concentrated, then acidified with 1 M HCl, extracted with EtOAc (10 mL), dried over MgSO4, filtered, concentrated and purified on reverse phase HPLC (H2O/MeCN gradient) to afford the title compound I1 as an off-white solid: 1H-NMR (400 MHz, CD3CN) δ=7.61 (s, 1H), 7.57 (m, 1H), 7.38 (m, 5H), 7.33 (d, J=2.4 Hz, 1H), 7.28 (m, 2H), 7.20 (dd, J=9.2, 2.8 Hz, 1H), 7.16 (t, J=5.2 Hz, NH), 6.90 (d, J=8.8 Hz, 1H), 4.04 (t, J=5.2 Hz, 2H), 3.63 (q, J=5.2 Hz, 2H), 3.59 (s, 2H). MS calculated for C26H21Cl2N2O5 (M+H+) 511.0, found 511.0.

Workup

  1. concentrationThe mixture is concentrated
  2. extractionextracted with EtOAc (10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified on reverse phase HPLC (H2O/MeCN gradient)

Sources & evidence

ORD record
ord-096ed385e9a042829d71e7a911a0b475
Source dataset
uspto-grants-2010_10
Patent number
US07820705B2

Reaction notes

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