Ethanol → 3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid

HRID 1430984Notes

Reaction equation

HRID 1430984 reaction equation
C[O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][C:13]2[CH:17]=[CH:16][S:15][CH:14]=2)[CH:7]=[C:6]([O:18][CH:19]([CH3:21])[CH3:20])[CH:5]=1.CCO.O.[OH-].[Na+]>C1COCC1>[CH:19]([O:18][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([O:10][CH2:11][CH2:12][C:13]2[CH:17]=[CH:16][S:15][CH:14]=2)[CH:7]=1)[C:3]([OH:22])=[O:2])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 14798Sodium HydroxideHCID 585289273-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid methyl ester

Product 1

HCID 585289133-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acidYield 90.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid methyl ester (5.24 g, 16.4 mmol) in THF (120 mL) was added EtOH (80 mL) and water (40 mL) at rt. Sodium hydroxide solution (1.0 M, 49.1 mL) was added slowly with some external cooling if needed. The mixture was stirred at rt overnight. On the second day organic solvents were removed by evaporation. The residue was partitioned between ether and water. After the ether layer was discarded, the aqueous layer was acidified with HCl (6.0 M, ˜8.2 mL) to pH<1, and extracted with EtOAc (3×). Combined EtOAc layers were washed with brine (1×), dried with anhydrous MgSO4, filtered, and concentrated to give 3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid (4.54 g, 90%) as a white solid. 1H NMR (300 MHz, CDCl3): δ 7.29 (dd, J=5, 3 Hz, 1H), 7.22-7.24 (m, 2H), 7.09-7.10 (m, 1H), 7.04 (dd, J=5, 1 Hz, 1H), 6.69 (m, 1H), 4.59 (m, 1H), 4.21 (t, J=7 Hz, 2H), 3.14 (t, 0.1=7 Hz, 2H), 1.35 (d, J=6 Hz, 6H).

Workup

  1. temperaturesome external cooling
  2. customOn the second day organic solvents were removed by evaporation
  3. customThe residue was partitioned between ether and water
  4. extractionextracted with EtOAc (3×)
  5. washCombined EtOAc layers were washed with brine (1×)
  6. dry with materialdried with anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-29d20490803b4cfc81b10ee795c0a290
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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