Water → 4-Chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid methyl ester

HRID 660973Notes

Reaction equation

HRID 660973 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([OH:13])=[O:12])[S:5][C:6]=1[CH:7]([OH:10])[CH2:8][CH3:9].[C:14]([O-])([O-])=O.[K+].[K+].IC.O>CN(C)C=O>[CH3:14][O:12][C:11]([C:4]1[S:5][C:6]([CH:7]([OH:10])[CH2:8][CH3:9])=[C:2]([Cl:1])[CH:3]=1)=[O:13]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 674852844-Chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid

Product 1

HCID 593559694-Chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid methyl esterYield 31.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of crude 4-chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid (0.262 g) in dimethylformamide (6.0 mL) is treated with K2CO3 (0.502 g, 3.63 mmol) and iodomethane (0.17 mL, 2.73 mmol) and stirred overnight. The reaction mixture is then poured into H2O (15 mL) and extracted with EtOAc (3×10 mL). Combined organic extracts are washed with brine (1×), dried over MgSO4, filtered, and concentrated. The residue is loaded onto silica gel and eluted with hexanes using a gradient of 0% to 50% EtOAc to provide 4-chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid methyl ester (87.6 mg, 15%-2 steps) as a yellow syrup. MS (ES): 216.9 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. washCombined organic extracts are washed with brine (1×)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted with hexanes using a gradient of 0% to 50% EtOAc

Sources & evidence

ORD record
ord-1f3c1003aef14d96bcf7be20d1003e50
Source dataset
uspto-grants-2011_12
Patent number
US08084489B2

Reaction notes

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