Water → [4-(4-Amino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

HRID 1468353Notes

Reaction equation

HRID 1468353 reaction equation
[CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:25])[CH:11]=2)[CH:6]=1.C1COCC1.[Cl-].[NH4+].O>CO.[Zn]>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:25])[CH:11]=2)[CH:6]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 86694945[6-Chloro-3-methyl-4-(4-nitro-phenyl)-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 86694946[4-(4-Amino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl esterYield 98.1%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

To a suspension of [6-chloro-3-methyl-4-(4-nitro-phenyl)-naphthalen-2-yl]-acetic acid methyl ester (133 mg, 0.36 mmol) in methanol (2 mL) was added THF (2 mL). Then, zinc dust (192.1 mg, 2.9 mmol) and ammonium chloride (192.6 mg, 3.6 mmol) were added followed by water (0.9 mL). The reaction mixture was stirred at room temperature for 10 minutes and TLC analysis of the mixture indicated the absence of starting material. The resulting solids were filtered and washed with ethyl acetate (20 mL). The solution was concentrated to remove organic solvent, then diluted with water (20 mL) and the mixture was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with brine solution (30 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent under vacuum gave [4-(4-amino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (120 mg, 97.9%) as a light brown oil which solidified slowly. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.90 (d, J=8.7 Hz, 1 H), 7.79 (s, 1 H), 7.43 (dd, J=8.7, 1.9 Hz, 1 H), 7.27 (d, J=1.9 Hz, 1 H), 6.85 (d, J=8.2 Hz, 2 H), 6.72 (d, J=8.2 Hz, 2 H), 5.26 (s, 2 H), 3.93 (s, 2 H), 3.64 (s, 3 H), 2.09 (s, 3 H). HRMS calcd. for C20H18ClNO2 [(M+H)+] 340.1099, obsd. 340.1097.

Workup

  1. filtrationThe resulting solids were filtered
  2. washwashed with ethyl acetate (20 mL)
  3. concentrationThe solution was concentrated
  4. customto remove organic solvent
  5. additiondiluted with water (20 mL)
  6. extractionthe mixture was extracted with ethyl acetate (2×20 mL)
  7. washThe combined organic extracts were washed with brine solution (30 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationFiltration of the drying agent and concentration of the solvent under vacuum

Sources & evidence

ORD record
ord-035ae36b9c4e41ce9ddcbf20d78add6b
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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