Lithium Hydroxide → {[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid

HRID 1665261Notes

Reaction equation

HRID 1665261 reaction equation
C([O:3][C:4](=[O:35])[CH2:5][N:6]([C:8](=[O:34])[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[C:28]([F:30])[C:27]([F:31])=[CH:26][C:25]=3[O:32][CH3:33])=[CH:20][CH:19]=2)[CH:10]=1)[CH3:7])C.[OH-].[Li+]>C1COCC1>[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:10]=[C:9]([CH:14]=[CH:13][C:12]=3[F:15])[C:8]([N:6]([CH2:5][C:4]([OH:35])=[O:3])[CH3:7])=[O:34])=[CH:23][CH:22]=2)=[C:25]([O:32][CH3:33])[CH:26]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67152333{[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid ethyl ester

Product 1

HCID 52933063{[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acidYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

{[3-(4′,5′-Difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid ethyl ester (0.29 g, 0.59 mmol) was dissolved in THF (25 mL) and lithium hydroxide solution (0.5N, 2 mL) was added. The mixture was stirred at room temperature for 2 hrs. Solvents were evaporated and the residue was treated with dilute hydrochloric acid and ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. Solvent was evaporated and the residue was dissolved in acetonitrile (1 mL) and diluted with water (8 mL). The mixture was lyophilized to give a fluffy solid as {[3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-4-fluoro-benzoyl]-methyl-amino}-acetic acid (0.26 g, 96%). HRMS (ES) calculated for C24H20F3NO5, 482.1186; found m/z 482.1185 [M+Na]+; 1H-NMR (DMSO-d6) δ ppm 12.86 (br s, 1H), 7.29-7.69 (m, 6H), 7.24 (dd, J=13.0, 7.2 Hz, 1H), 7.08 (d, J=8.5 Hz, 2H), 5.19 and 5.23 (s, 2H, rotamer), 3.97 and 4.14 (s, 2H, rotamer), 3.76 (s, 3H), 2.94 and 2.95 (s, 3H, rotamer).

Workup

  1. customSolvents were evaporated
  2. additionthe residue was treated with dilute hydrochloric acid and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customSolvent was evaporated
  6. dissolutionthe residue was dissolved in acetonitrile (1 mL)
  7. additiondiluted with water (8 mL)

Sources & evidence

ORD record
ord-5ba2498d5a1648dd9ab145a4d081e832
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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