Hydrochloric Acid → 4-(3-((5-Cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-3-fluorobenzoic acid

HRID 1748217Notes

Reaction equation

HRID 1748217 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:18])[F:17])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:28][CH:27]3[N:29]([C:30]4[CH:39]=[CH:38][C:33]([C:34]([O:36]C)=[O:35])=[CH:32][C:31]=4[F:40])[CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[CH2:3][CH2:2]1.CO.[OH-].[K+].Cl>O1CCCC1.C(OCC)(=O)C>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:18])([F:17])[F:19])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:23][CH:24]3[N:29]([C:30]4[CH:39]=[CH:38][C:33]([C:34]([OH:36])=[O:35])=[CH:32][C:31]=4[F:40])[CH:27]([CH2:26][CH2:25]3)[CH2:28]2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14797Potassium HydroxideHCID 67983240HCID 67983240, compound

Product 1

HCID 679850254-(3-((5-Cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-3-fluorobenzoic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

The ester above, methyl 4-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-3-fluorobenzoate (24 mg, 0.043 mmoles) was dissolved in tetrahydrofuran (0.5 mL) and methanol (0.5 mL) and subjected to an aqueous solution of potassium hydroxide (6 N aqueous solution, 0.5 mL, 3.0 mmoles). The mixture was heated to 70° C. for 2 hours and then cooled to RT. The pH of the solution was adjusted to 6 using aqueous HCl (0.5 mL of 6N). The mixture was diluted with ethyl acetate (20 mL), extracted and water washed (3×1 mL). The organics were dried (MgSO4) then evaporated in vacuo. The product crystallized upon concentration of the ethyl acetate mother liquor, was washed with sparing ice cold ethyl acetate (0.5 mL), and the white solid dried to give the title compound.

Workup

  1. temperaturecooled to RT
  2. extractionextracted
  3. washwater washed (3×1 mL)
  4. dry with materialThe organics were dried (MgSO4)
  5. customthen evaporated in vacuo
  6. customThe product crystallized upon concentration of the ethyl acetate mother liquor
  7. washwas washed with sparing ice cold ethyl acetate (0.5 mL)
  8. customthe white solid dried

Sources & evidence

ORD record
ord-ed33e7ec382c4564a15c6a9cd32dfbcc
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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