Ethylene Glycol → (1S)-1-{2-[(6-bromo-2-naphthyl)thio]phenyl}ethanol

HRID 735314Notes

Reaction equation

HRID 735314 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([SH:12])[CH:6]=[CH:5]2.I[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C@@H:20]([OH:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+].C(O)CO>C(OCC)(=O)C.[Cu]I.C(O)(C)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C@@H:20]([OH:22])[CH3:21])[CH:6]=[CH:5]2

Participants

8

Reactant 4

HCID 174Ethylene GlycolHCID 11430Potassium CarbonateHCID 10514669(1S)-1-(2-iodophenyl)ethanolHCID 197648176-Bromonaphthalene-2-thiol

Product 1

HCID 68901000(1S)-1-{2-[(6-bromo-2-naphthyl)thio]phenyl}ethanolYield 87.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-2-naphthyl hydrosulfide (Example 5 Step 2, 1.80 g, 7.53 mmol), (1S)-1-(2-iodophenyl)ethanol (1.82 g, 7.34 mmol), copper(I) iodide (70 mg, 0.37 mmol) and potassium carbonate (2.02 g, 14.6 mmol) was degassed then isopropyl alcohol (10 mL) and ethylene glycol (0.82 mL, 14.7 mmol) added. The reaction was heated to 80° C. overnight. The cooled reaction mixture was diluted with ethyl acetate (40 mL), filtered and concentrated in vacuo. The residue was purified by flash column chromatography, eluting with a 10-20% ethyl acetate/isohexane gradient to give solid (1S)-1-{2-[(6-bromo-2-naphthyl)thio]phenyl}ethanol (2.30 g, 85%). 1H NMR (400 MHz, CDCl3) δ 7.94 (1H, s), 7.68 (1H, dd, J 1.4, 7.8), 7.64 (1H, d, J 8.7 Hz), 7.58-7.50 (3H, m), 7.43-7.39 (1H, m), 7.36 (1H, dd, J 1.4, 7.8 Hz), 7.30 (1H, dd, J 1.8, 8.6 Hz), 7.27-7.23 (1H, m), 5.44 (1H, q, J 6.3 Hz), 1.46 (3H, d, J 6.4 Hz); m/z (ES+) 341, 343 [(M-OH)+].

Workup

  1. customwas degassed
  2. customThe cooled reaction mixture
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography
  6. washeluting with a 10-20% ethyl acetate/isohexane gradient

Sources & evidence

ORD record
ord-d9eb73f9877048faa7581dff3ef5c32a
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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