Triphenylphosphine → 3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid methyl ester

HRID 1430983Notes

Reaction equation

HRID 1430983 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([O:10][CH:11]([CH3:13])[CH3:12])[CH:7]=[C:6]([OH:14])[CH:5]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[S:35]1[CH:39]=[CH:38][C:37]([CH2:40][CH2:41]O)=[CH:36]1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:5]=[C:6]([O:14][CH2:41][CH2:40][C:37]2[CH:38]=[CH:39][S:35][CH:36]=2)[CH:7]=[C:8]([O:10][CH:11]([CH3:13])[CH3:12])[CH:9]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 83731Thiophene-3-ethanolHCID 5363146Diisopropyl azodicarboxylateHCID 23072925Methyl 3-hydroxy-5-isopropoxybenzoate

Product 1

HCID 585289273-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid methyl esterYield 91.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-hydroxy-5-isopropoxy-benzoic acid methyl ester (3.76 g, 17.9 mmol) in THF (100 mL) at rt was added PPh3 (4.93 g, 18.8 mmol) and 2-(3-thienyl)ethanol (2.10 mL, 18.8 mmol). DIAD (3.71 mL, 18.8 mmol) was added dropwise at rt with external cooling to keep the solvent from boiling off. The resulting mixture was stirred at rt for 3 hr and concentrated to give a residue which was purified by silica gel chromatography (5×25 cm, hexane/EtOAc, v/v=10:1, 5:1). Fractions containing the product were pooled and concentrated to give 3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid methyl ester (5.24 g, 91%) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.28 (dd, J=5, 3 Hz, 1H), 7.15-7.18 (m, 2H), 7.08-7.09 (m, 1), 7.03 (dd, J=5, 1 Hz, 1H), 6.63 (m, 1H), 4.58 (m, 1H), 4.19 (t, J=7 Hz, 2H), 3.89 (s, 3H), 3.12 (t, 1=7 Hz, 2H), 1.33 (d, J=6 Hz, 6H).

Workup

  1. temperaturewith external cooling
  2. concentrationconcentrated
  3. customto give a residue which
  4. customwas purified by silica gel chromatography (5×25 cm, hexane/EtOAc, v/v=10:1, 5:1)
  5. additionFractions containing the product
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ed4054a6b08c48f09a11d30692ca3c2b
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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