Potassium Iodide → 4-(3,5-Bis-hydroxymethyl-phenoxy)-butyric acid methyl ester

HRID 1950751Notes

Reaction equation

HRID 1950751 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([OH:11])[CH:6]=[C:7]([CH2:9][OH:10])[CH:8]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+].[CH3:20][O:21][C:22](=[O:27])[CH2:23][CH2:24][CH2:25]Br>C1COCC1>[CH3:20][O:21][C:22](=[O:27])[CH2:23][CH2:24][CH2:25][O:11][C:5]1[CH:4]=[C:3]([CH2:2][OH:1])[CH:8]=[C:7]([CH2:9][OH:10])[CH:6]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 107604Methyl 4-bromobutyrateHCID 15194153,5-Di(hydroxymethyl)phenol

Product 1

HCID 594401374-(3,5-Bis-hydroxymethyl-phenoxy)-butyric acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,5-bis-hydroxymethylphenol (Felder, D.; Gutiérrez Nava, M.; del Pilar Carreon, M.; Eckert, J. F.; Luccisano, M.; Schell, C.; Masson, P.; Gallani, J. L.; Heinrich, B.; Guillon, D.; Nierengarten, J. F. Helv. Chimica Acta 2002, 85, 288) (200 mg), potassium iodide (50 mg) and potassium carbonate (540 mg) in THF (2.5 mL) was added 4-bromo-butyric acid methyl ester (400 μL). The reaction mixture was stirred for 20 h at room temperature then the unsoluble part was filtered off. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography (Merck SuperVarioFlash 30 g column, Si60 15-40 μm), using gradient elution with a mixture of MeOH (A)/DMC (B), (gradient: 100% B down to 5% A: 95% B) to give 4-(3,5-bis-hydroxymethyl-phenoxy)-butyric acid methyl ester (53.5 mg): LC/MS (Method A2: ES: m/z=255 MH+; m/z=237 (M+H−H2O)+; RT=2.5 min; 1H N.M.R. (400 MHz, DMSO-d6, δ in ppm): δ=1.96 (m, 2H); 2.47 (t, J=6.5 Hz, 2H); 3.61 (s, 3H); 3.96 (t, J=6.5 Hz, 2H); 4.43 (d, J=6.0 Hz, 4H); 5.11 (t, J=6.0 Hz, 2H); 6.71 (s, 2H); 6.82 (s, 1H).

Workup

  1. filtrationthe unsoluble part was filtered off
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by silica gel chromatography (Merck SuperVarioFlash 30 g column, Si60 15-40 μm)
  4. washelution
  5. additionwith a mixture of MeOH (A)/DMC (B), (gradient: 100% B down to 5% A: 95% B)

Sources & evidence

ORD record
ord-c74fea9323964b72aa51d5fb0572220a
Source dataset
uspto-grants-2013_03
Patent number
US08404678B2

Reaction notes

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