Hydrochloric Acid → 4-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepan-1-yl}-benzoic acid

HRID 1689826Notes

Reaction equation

HRID 1689826 reaction equation
C([O:3][C:4](=[O:36])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:17][CH2:16][CH2:15][CH:14]([O:18][CH2:19][C:20]3[C:21]([C:28]4[C:33]([Cl:34])=[CH:32][CH:31]=[CH:30][C:29]=4[Cl:35])=[N:22][O:23][C:24]=3[CH:25]3[CH2:27][CH2:26]3)[CH2:13][CH2:12]2)=[CH:7][CH:6]=1)C.[OH-].[K+].Cl>C(O)C.O1CCCC1>[CH:25]1([C:24]2[O:23][N:22]=[C:21]([C:28]3[C:29]([Cl:35])=[CH:30][CH:31]=[CH:32][C:33]=3[Cl:34])[C:20]=2[CH2:19][O:18][CH:14]2[CH2:15][CH2:16][CH2:17][N:11]([C:8]3[CH:7]=[CH:6][C:5]([C:4]([OH:36])=[O:3])=[CH:10][CH:9]=3)[CH2:12][CH2:13]2)[CH2:27][CH2:26]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 59369326HCID 59369326, compound

Product 1

HCID 252047654-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepan-1-yl}-benzoic acidYield 99%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 8.28 g (15.64 mmol) of 4-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepan-1-yl}-benzoic acid ethyl ester (Isomer B) in 50 mL of Ethanol and 150 mL of tetrahydrofuran, is added potassium hydroxide (55.16 g, 78.19 mmol). The resulting mixture is stirred at 60° C. for 14 hours. The mixture is cooled to room temperature and acidified with 2N HCl to pH 5-6. The solvent is removed under vacuum, the resulting slurry is diluted with CH2Cl2 (150 mL) and washed with water (2×80 mL). The organic layer is dried (MgSO4), filtered and concentrated to afford 7.76 g of the title compound as a white solid (98%). MS (m/e): 501 (M+1).

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. customThe solvent is removed under vacuum
  3. additionthe resulting slurry is diluted with CH2Cl2 (150 mL)
  4. washwashed with water (2×80 mL)
  5. dry with materialThe organic layer is dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2604137ef5874f38928870656924b27c
Source dataset
uspto-grants-2012_04
Patent number
US08153624B2

Reaction notes

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