Acetonitrile → [4-(4-Acetylamino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid

HRID 1468460Notes

Reaction equation

HRID 1468460 reaction equation
C[O:2][C:3](=[O:27])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:25])[CH3:24])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:26])[CH:11]=2)[CH:6]=1.[OH-].[Na+].C(#N)C>C(O)C.C1COCC1>[C:23]([NH:22][C:19]1[CH:18]=[CH:17][C:16]([C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([Cl:26])[CH:11]=3)[CH:6]=[C:5]([CH2:4][C:3]([OH:27])=[O:2])[C:14]=2[CH3:15])=[CH:21][CH:20]=1)(=[O:25])[CH3:24]

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 86695034[4-(4-Acetylamino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 71711713[4-(4-Acetylamino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acidYield 60.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [4-(4-acetylamino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (112 mg, 0.29 mmol) in ethanol (3 mL) and THF (3 mL) was added a sodium hydroxide solution (586 uL, 1.0 N) at room temperature. The resulting clear solution was stirred for 4 h. Then, the solvents were removed under vacuum and the residue was diluted with water (10 mL), acidified with 1.0 N hydrochloric acid, and extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with brine solution (20 mL) and dried over anhydrous magnesium sulfate. Filtration of drying agent and concentration of the solvent under vacuum gave a solid which was treated with hot acetonitrile. After cooling in the refrigerator, the solids were collected by filtration and washed with acetonitrile to give [4-(4-acetylamino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid (65 mg, 60.2%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.50 (s, 1 H), 10.13 (s, 1 H), 7.93 (d, J=8.8 Hz, 1 H), 7.84 (s, 1 H), 7.76 (d, J=8.2 Hz, 2 H), 7.45 (dd, J=8.8, 1.8 Hz, 1 H), 7.15 (m, 3 H), 3.84 (s, 2 H), 2.10 (br. s., 3 H), 2.09 (br. s., 3 H). HRMS (ES+) calcd. for C21H19ClNO3 [(M+H)+] 368.1048, obsd. 368.1049.

Workup

  1. customThen, the solvents were removed under vacuum
  2. additionthe residue was diluted with water (10 mL)
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. washThe combined organic extracts were washed with brine solution (20 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationFiltration
  7. customof drying agent and concentration of the solvent under vacuum
  8. customgave a solid which
  9. temperatureAfter cooling in the refrigerator
  10. filtrationthe solids were collected by filtration
  11. washwashed with acetonitrile

Sources & evidence

ORD record
ord-85cc3f3e31be4e2597c9c73f4ebc7d29
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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