Hydrochloric Acid → 3-[4-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indazol-1-yl]-propionic acid

HRID 551496Notes

Reaction equation

HRID 551496 reaction equation
C([O:3][C:4](=[O:34])[CH2:5][CH2:6][N:7]1[C:15]2[C:10](=[C:11]([CH2:16][O:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]4[CH:29]=[C:28]([F:30])[C:27]([F:31])=[CH:26][C:25]=4[O:32][CH3:33])=[CH:20][CH:19]=3)[CH:12]=[CH:13][CH:14]=2)[CH:9]=[N:8]1)C.O.[OH-].[Li+].CCOC(C)=O.Cl>C1COCC1.O>[F:31][C:27]1[C:28]([F:30])=[CH:29][C:24]([C:21]2[CH:20]=[CH:19][C:18]([O:17][CH2:16][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:10]=3[CH:9]=[N:8][N:7]4[CH2:6][CH2:5][C:4]([OH:34])=[O:3])=[CH:23][CH:22]=2)=[C:25]([O:32][CH3:33])[CH:26]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 168937Lithium hydroxide, monohydrateHCID 671514693-[4-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indazol-1-yl]-propionic acid ethyl ester2×

Product 1

HCID 529396113-[4-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-indazol-1-yl]-propionic acidYield 59.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-[4-(4′,5′-Difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-indazol-1-yl]-propionic acid ethyl ester (0.095 g, 0.204 mmol) and lithium hydroxide hydrate (10 mg, 0.245 mmol) in 5 mL THF/1 mL H2O was stirred at RT for 3 hrs. The reaction was distributed between EtOAc and H2O. The water layer was made acidic to pH 3 with 1N HCl and the organic layer was separated and concentrated in vacuo. The crude product was purified by flash chromatography with a gradient from 0-3% methanol in CH2Cl2 to yield 3-[4-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-indazol-1-yl]-propionic acid as a white solid (53 mg, 59%). LC-MS (ES) calculated for C24H20F2N2O04, 438.43; found m/z 439 [M+H]+.

Workup

  1. customthe organic layer was separated
  2. concentrationconcentrated in vacuo
  3. customThe crude product was purified by flash chromatography with a gradient from 0-3% methanol in CH2Cl2

Sources & evidence

ORD record
ord-233f2797c4f34e53bbac1eb74bb04140
Source dataset
uspto-grants-2011_05
Patent number
US07947728B1

Reaction notes

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