Hydrochloric Acid → 2-Methyl-6-[3-(quinolin-2-ylmethoxy)-phenoxymethyl]-benzoic acid

HRID 892135Notes

Reaction equation

HRID 892135 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH2:21][C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]=3)[CH:15]=2)[C:3]=1[C:4]([O:6]C)=[O:5].[OH-].[Na+].Cl>C(O)C>[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH2:21][C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]=3)[CH:15]=2)[C:3]=1[C:4]([OH:6])=[O:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 22241476Methyl 2-methyl-6-[3-(quinolin-2-ylmethoxy)-phenoxymethyl]-benzoate

Product 1

HCID 98010622-Methyl-6-[3-(quinolin-2-ylmethoxy)-phenoxymethyl]-benzoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of methyl 2-methyl-6-[3-(quinolin-2-ylmethoxy)-phenoxymethyl]-benzoate (1.6 g, 3.8 mmol, example 4) in ethanol (25 mL) is heated with a 10N sodium hydroxide solution (4.0 mL, 40 mmol) at 70° C. for 14 h. The reaction is cooled, neutralized with a 2N HCl solution (20 mL) and concentrated to remove the ethanol. Ethyl acetate is added and washed with water. The aqueous layer is saturated with sodium chloride and back extracted with ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and concentrated to yield a crude solid. The solid is purified by column chromatography (silica, 5 to 10% methanol in dichloromethane) to provide the title compound. An analytically pure sample is prepared by recystallization from methanol: m.p. 167–168° C., 1H NMR (300 MHz, CDCl3)δ0.15 (d, 2H), 7.80 (d, 1H), 7.71 (t, 1H), 7.61–7.51 (m, 2H), 7.26–7.10 (m, 3H), 7.00 (t, 1H), 6.66 (s, 1H), 6.52 (d, 1H), 6.46 (d, 1H), 5.26 (s, 2H), 5.15 (s, 2H), 2.44 (s, 3H); MS (ESI) 400 (M+H)+.

Workup

  1. temperatureThe reaction is cooled
  2. concentrationconcentrated
  3. customto remove the ethanol
  4. additionEthyl acetate is added
  5. washwashed with water
  6. extractionback extracted with ethyl acetate
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield a crude solid
  11. customThe solid is purified by column chromatography (silica, 5 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-57bc8147fd3e439cb9f3fc9ae236da54
Source dataset
uspto-grants-2006_02
Patent number
US07005440B1

Reaction notes

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