3-Fluoro-4-hydroxybenzeneacetic acid → Methyl 2-(3-fluoro-4-hydroxyphenyl)acetate

HRID 2377934Notes

Reaction equation

HRID 2377934 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=[O:11])[CH:5]=[CH:6][C:7]=1[OH:8].[C:13]([O-])(O)=O.[Na+]>CO.OS(O)(=O)=O>[CH3:13][O:11][C:10](=[O:12])[CH2:9][C:4]1[CH:5]=[CH:6][C:7]([OH:8])=[C:2]([F:1])[CH:3]=1

Participants

5

Reactant 2

HCID 680143-Fluoro-4-hydroxybenzeneacetic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 10797559Methyl 2-(3-fluoro-4-hydroxyphenyl)acetateYield 181.5%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidCatalystHCID 887MethanolSolvent

Procedure

To a solution of (3-fluoro-4-hydroxy-phenyl)-acetic acid (20 g, 117.5 mmol) in MeOH (150 mL), was H2SO4 (3 drops) added. The reaction mixture was heated to reflux and maintained for 2 hours. The reaction was cooled to room temperature and 5 g of NaHCO3 was added portionwise. The reaction was concentrated under vacuum and dissolved in ether (200 mL). The ether layer was washed with sat. NaHCO3. The ether layer was dried over MgSO4, and concentrated under vacuum to afford the desired compound (19.9 g, 92%) as an oil. The crude compound was used for the next step without further purification. 1H NMR (400 Mz, DMSO-d6) δ 9.92 (s, 1H), 7.01-7.20 (m, 2H), 3.62 (s, 2H), 3.61 (s, 3H). LCMS 185.1 [MH+].

Workup

  1. additionadded
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux
  4. temperaturemaintained for 2 hours
  5. concentrationThe reaction was concentrated under vacuum
  6. dissolutiondissolved in ether (200 mL)
  7. washThe ether layer was washed with sat. NaHCO3
  8. dry with materialThe ether layer was dried over MgSO4
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-2ac60c0e4cd04ae0956e689cee0f706f
Source dataset
uspto-grants-2008_12
Patent number
US07470699B2

Reaction notes

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