Hydrochloric Acid → 2-Methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid

HRID 923560Notes

Reaction equation

HRID 923560 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=1.[NH2:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24]C)=[O:23])=[C:20]([O:28][CH3:29])[CH:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Li+].[OH-].Cl>CN(C=O)C.CC(=O)OCC.C1COCC1.CO>[CH3:29][O:28][C:20]1[CH:19]=[C:18]([NH:17][C:10](=[O:12])[CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=2[C:13]([F:16])([F:15])[F:14])[CH:27]=[CH:26][C:21]=1[C:22]([OH:24])=[O:23]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 168705Methyl 4-amino-o-anisateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 467375752-(4-Methoxy-2-(trifluoromethyl)phenyl)acetic acid

Product 1

HCID 710767972-Methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acidYield 49.3%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared using General Procedures 6 and 9: To a stirred solution of 2-(4-methoxy-2-(trifluoromethyl)phenyl)acetic acid (500 mg, 2.14 mmol), methyl 4-amino-2-methoxybenzoate (387 mg, 2.14 mmol) and TEA (744 μL, 5.34 mmol) in DMF (5 mL) was added HATU (852 mg, 2.24 mmol). After 1 h the reaction mixture was diluted with EA (100 mL) and washed with brine (2×100 mL). The organic layer was pre-absorbed onto silica gel and then purified by chromatography (EA/isohexanes) to afford a white solid. The solid was diluted with THF (15 mL) and MeOH (10 mL) and then 1 N LiOH (427 μl, 4.27 mmol) was added and the solution stirred at room temperature. After 18 h the reaction mixture was acidified by the addition of 1 N HCl (50 mL) and the organics removed under vacuum. The residue was extracted with EA (100 mL) and the organics were washed with brine (200 mL) and dried over magnesium sulfate. The solvent was concentrated to afford 404 mg (49%) 2-methoxy-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid INT-23 as a white powder. LCMS-ESI (m/z) calculated for C18H16F3NO5: 237 found 236 [M−H]−, tR=1.90 min (Method 10).

Workup

  1. customPrepared
  2. washwashed with brine (2×100 mL)
  3. customThe organic layer was pre-absorbed onto silica gel
  4. custompurified by chromatography (EA/isohexanes)
  5. customto afford a white solid
  6. customthe organics removed under vacuum
  7. extractionThe residue was extracted with EA (100 mL)
  8. washthe organics were washed with brine (200 mL)
  9. dry with materialdried over magnesium sulfate
  10. concentrationThe solvent was concentrated

Sources & evidence

ORD record
ord-7bad19e86d6a43d6ab84d0964d92978d
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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