Methanol → Methyl 5-(hydroxymethyl)thiophene-3-carboxylate

HRID 900991Notes

Reaction equation

HRID 900991 reaction equation
[OH:1][CH2:2][C:3]1[S:7][CH:6]=[C:5]([C:8]([OH:10])=[O:9])[CH:4]=1.OS(O)(=O)=O.[CH3:16]O>O>[CH3:16][O:9][C:8]([C:5]1[CH:4]=[C:3]([CH2:2][OH:1])[S:7][CH:6]=1)=[O:10]

Participants

5

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 596988145-(Hydroxymethyl)thiophene-3-carboxylic acid

Product 1

HCID 12926498Methyl 5-(hydroxymethyl)thiophene-3-carboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 5-hydroxymethyl-thiophene-3-carboxylic acid (14.5 g, 91.7 mmol), concentrated H2SO4 (5.2 mL, 93.5 mmol) and methanol (250 mL) is heated to reflux for 3.5 h. After cooling, the mixture is poured into water and extracted with dichloromethane (3×). The combined extracts are washed successively with saturated aq NaCl, aq NaHCO3 and water followed by drying over Na2SO4, filtration and concentration in vacuo. The residue is purified by distillation to give 5-hydroxymethyl-thiophene-3-carboxylic acid methyl ester (8.8 g, 56%) as a clear oil: bp 155-157° C./6-7 mbar; 1H NMR (CDCl3, 300 MHz) δ 7.98 (s, 1 H), 7.35 (s, 1 H), 4.78 (s, 2 H), 3.80 (s, 3 H), 2.63 (s, 1 H).

Workup

  1. temperatureis heated
  2. temperatureto reflux for 3.5 h
  3. temperatureAfter cooling
  4. extractionextracted with dichloromethane (3×)
  5. washThe combined extracts are washed successively with saturated aq NaCl, aq NaHCO3 and water
  6. dry with materialby drying over Na2SO4, filtration and concentration in vacuo
  7. distillationThe residue is purified by distillation

Sources & evidence

ORD record
ord-3dd799c5a07f4d37b79975286dcbaaa3
Source dataset
uspto-grants-2008_04
Patent number
US07361671B2

Reaction notes

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