Water → 5-Formyl-2-hydroxy-3-methyl-benzoic acid methyl ester

HRID 1047892Notes

Reaction equation

HRID 1047892 reaction equation
C1N2CN3CN(C2)CN1C3.[CH3:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[C:15]=1[OH:21].O.[C:24](O)(C(F)(F)F)=[O:25]>>[CH3:11][O:12][C:13](=[O:22])[C:14]1[CH:19]=[C:18]([CH:24]=[O:25])[CH:17]=[C:16]([CH3:20])[C:15]=1[OH:21]

Participants

5

Reactant 4

HCID 962WaterHCID 4101HexamethylenetetramineHCID 6422Trifluoroacetic acidHCID 31835Benzoic acid, 2-hydroxy-3-methyl-, methyl ester

Product 1

HCID 593141335-Formyl-2-hydroxy-3-methyl-benzoic acid methyl esterYield 86%

Conditions

Temperature
78 °C

Procedure

To a solution of HMTA (1,3,5,7-Tetraaza-tricyclo[3.3.1.13,7]decane, 8.43 g, 60.2 mmol) in TFA (100 mL) is added 2-hydroxy-3-methyl-benzoic acid methyl ester (5 g, 30.1 mmol) and the reaction is refluxed (78° C.) overnight. The reaction is cooled to 50° C. and water (400 mL) is added with stirring. The mixture is stirred at 50° C. for 2 h then cooled to RT and extracted with EtOAc (2×200 mL). The combined organic layers are washed with brine (75 mL), dried over anhydrous MgSO4 and concentrated in vacuo. The residue is purified by flash column chromatography (120 silica gel, gradient elution: 0-50% EtOAc in heptane) to give product (281) as off-white solid (5.05 g, 86%).

Workup

  1. temperatureThe reaction is cooled to 50° C.
  2. stirringThe mixture is stirred at 50° C. for 2 h
  3. temperaturethen cooled to RT
  4. extractionextracted with EtOAc (2×200 mL)
  5. washThe combined organic layers are washed with brine (75 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by flash column chromatography (120 silica gel, gradient elution: 0-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-78be59dd77464d4e92b42513dbfa6909
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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