Methanol → Methyl 5-chloro-3-hydroxy-2-methylbenzoate

HRID 1050442Notes

Reaction equation

HRID 1050442 reaction equation
S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:7]=[C:8]([OH:16])[C:9]([CH3:15])=[C:10]([CH:14]=1)[C:11]([OH:13])=[O:12].[CH3:17]O>>[Cl:5][C:6]1[CH:7]=[C:8]([OH:16])[C:9]([CH3:15])=[C:10]([CH:14]=1)[C:11]([O:13][CH3:17])=[O:12]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 902730075-Chloro-3-hydroxy-2-methylbenzoic acid

Product 1

HCID 70904667Methyl 5-chloro-3-hydroxy-2-methylbenzoateYield 64.7%

Procedure

To cold (0° C. ice bath) methanol (200 mL) with stirring was added drop-wise thionyl chloride (12 mL, 164 mmol). The reaction was maintained for 15 minutes, at which time 5-chloro-3-hydroxy-2-methylbenzoic acid (6.5 g, 34.8 mmol) was added. The reaction was allowed to warm to room temperature and maintained overnight. The reaction was evaporated to dryness under vacuum and the residue was purified by silica gel chromatography (Analogix, SF40-150 g, 50 to 100% CH2Cl2 in hexanes). An overlap fraction containing a close faster running impurity was combined and repurified to give more pure product. The combined pure fractions were evaporated to dryness to give methyl 5-chloro-3-hydroxy-2-methylbenzoate (4.52 g, 22.53 mmol, 64.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 10.29 (s, 1H), 7.18 (d, J=2.02 Hz, 1H), 7.01 (d, J=2.27 Hz, 1H), 3.82 (s, 3H), 2.25 (s, 3H). MS(ES) [M+H]+ 201.0.

Workup

  1. additionwas added
  2. temperaturemaintained overnight
  3. customThe reaction was evaporated to dryness under vacuum
  4. customthe residue was purified by silica gel chromatography (Analogix
  5. additionAn overlap fraction containing
  6. customa close faster
  7. customrepurified
  8. customto give more pure product
  9. customThe combined pure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-fca0e898d4424d05818f4b7902788195
Source dataset
uspto-grants-2016_07
Patent number
US09382234B2

Reaction notes

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