Anisole → HCID 58902359, compound

HRID 1640124Notes

Reaction equation

HRID 1640124 reaction equation
COC1C=CC(C[NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=CC=1.C1(OC)C=CC=CC=1.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[CH:25]=[C:24]3[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]3)=[CH:18][CH:17]=2)[CH:12]=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 7519AnisoleHCID 9845Trifluoroacetic anhydrideHCID 589023857-({2-[(4-Methoxybenzyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid

Product 1

HCID 58902359HCID 58902359, compoundYield 94.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 7-({2-[(4-methoxybenzyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (21.5 g, 0.0532 mol), anisole (52 mL, 0.48 mol) and TFAA (100 mL, 2 mol) in DCM (400 mL) was stirred at 37° C. overnight. The solvent was removed by evaporation at 30° C. To the resulting mixture was added 1N NaOH (300 mL) and the solution was extracted with ether. The aqueous solution was acidified with conc. HCl to pH=3. The water layer was discarded, the residue was washed with water (3×). The solid was dried in vacuo overnight to give 7-[(2-aminopyridin-4-yl)oxy]-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (14.3 g). The combined yield for steps 2 and 3 was 94%. 1H NMR (DMSO-d6, 400 MHz) 7.83 (d, 1H); 7.30 (s, 2H); 7.20 (d, 1H); 6.98 d, 1H); 6.95 (dd, 1H); 6.46 (dd, 1H); 5.95 (d, 1H); 3.70 (s, 2H); 2.60-3.00 (m, 5H); 2.09 (m, 1H); 1.72 (m, 1H). LCMS ES+ 285.3.

Workup

  1. customThe solvent was removed by evaporation at 30° C
  2. additionTo the resulting mixture was added 1N NaOH (300 mL)
  3. extractionthe solution was extracted with ether
  4. washthe residue was washed with water (3×)
  5. customThe solid was dried in vacuo overnight

Sources & evidence

ORD record
ord-958c40b07ac34116a2b7c3067bdb0c42
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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