Ethylene Glycol → 2-[3-(2-Methoxyphenylsulfonyloxy)-5-methylphenoxy]ethanol

HRID 442960Notes

Reaction equation

HRID 442960 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([O:12][C:13]1[CH:14]=[C:15]([OH:20])[CH:16]=[C:17]([CH3:19])[CH:18]=1)(=[O:11])=[O:10].[CH2:21](O)[CH2:22][OH:23].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>C(OCC)C.O1CCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([O:12][C:13]1[CH:14]=[C:15]([CH:16]=[C:17]([CH3:19])[CH:18]=1)[O:20][CH2:21][CH2:22][OH:23])(=[O:10])=[O:11]

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 13831Tributylphosphine3×HCID 730421,1'-(Azodicarbonyl)dipiperidine3×HCID 227224733-(2-Methoxyphenylsulfonyloxy)-5-methylphenol

Product 1

HCID 541437062-[3-(2-Methoxyphenylsulfonyloxy)-5-methylphenoxy]ethanolYield 67.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-(2-methoxyphenylsulfonyloxy)-5-methylphenol (245 mg, 0.83 mmol, prepared in step b of example 8), ethylene glycol (0.23 mL, 4.1 mmol), 1,1'-(azodicarbonyl)dipiperidine (420 mg, 1.66 mmol) and anhydrous tetrahydrofuran (6 mL) was cooled to 0° C. under nitrogen. Tri-n-butylphosphine (0.41 mL, 1.66 mmol) was added dropwise over 2.5 minutes. The mixture was stirred at 0° C. for 5 hours, then more 1,1'-(azodicarbonyl)dipiperidine (210 mg) and tri-n-butylphosphine (0.21 mL) were added. The reaction was stirred overnight at ambient temperature, then more 1,1'-(azodicarbonyl)dipiperidine (420 mg) and tri-n-butylphosphine (0.41 mL) were added. The mixture was stirred overnight at ambient temperature, then diethyl ether (50 mL) was added and the mixture was filtered. The filtrate was concentrated, and the residue was purified by flash column chromatography through silica gel (3:2 ethyl acetate/hexane) to give the title compound as a colorless oil (190 mg, 67%). 1H-NMR (300 MHz, CDCl3) δ 7.82 (dd, 1H, J=1.7, 7.9 Hz), 7.62 (ddd, 1H, J=1.8, 7.4, 8.4 Hz), 7.09 (dd, 1H, J=0.8, 8.4 Hz), 6.99-7.05 (m, 1H), 6.60-6.61 (m, 1H), 6.53-6.55 (m, 1H), 6.46-6.48 (m, 1H), 4.02 (s, 3H), 3.89-4.01 (m, 4H), 2.25 (d, 3H, J=0.6 Hz). Mass spectrum (MALDI-TOF, α-cyano-4-hydroxycinnamic acid matrix) calcd. for C16H18O6S: 361.1 (M+Na). Found: 360.6.

Workup

  1. stirringThe reaction was stirred overnight at ambient temperature
  2. stirringThe mixture was stirred overnight at ambient temperature
  3. filtrationthe mixture was filtered
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by flash column chromatography through silica gel (3:2 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-cf3254badb4142aba087a9e80192838c
Source dataset
uspto-grants-1999_04
Patent number
US05891909

Reaction notes

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