Ammonia → (1S)-1-(2-{[6-(2,4-Difluorophenyl)-2-naphthyl]sulfonyl}phenyl)ethanol

HRID 735313

Reaction equation

HRID 735313 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([S:19]([O-:21])=[O:20])[CH:13]=[CH:12]2.[Na+].Br[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C@@H:30]([OH:32])[CH3:31].N>CS(C)=O.[Cu]I>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([S:19]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C@@H:30]([OH:32])[CH3:31])(=[O:21])=[O:20])[CH:13]=[CH:12]2

Participants

6

Reactant 3

HCID 222AmmoniaHCID 69503311-(2-Bromophenyl)ethan-1-olHCID 68899091HCID 68899091, compound

Product 1

HCID 68901134(1S)-1-(2-{[6-(2,4-Difluorophenyl)-2-naphthyl]sulfonyl}phenyl)ethanolYield 26.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

Sodium 6-(2,4-difluorophenyl)naphthalene-2-sulfinate (Step 3, 486 mg, 1.49 mmol), (1S)-1-(2-bromophenyl)ethanol (260 mg, 1.29 mmol) and copper(I) iodide (1.23 g, 6.46 mmol) were combined in dimethylsulfoxide (10 mL) and degassed. The reaction was heated to 110° C. for 2 hours. The cooled reaction mixture was poured into conc. ammonia solution and extracted with diethyl ether (x4). The combined organic layers were washed with brine, dried over MgSO4 and evaporated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 5% then 10% diethyl ether/dichloromethane, followed by trituration with isohexane. A second column, eluting with 60% diethyl ether/isohexane, followed by trituration with isohexane, gave the title compound (145 mg). 1H NMR (500 MHz, CDCl3) δ 8.56 (1H, s), 8.17 (1H, d, J=7.9 Hz), 8.06-7.98 (3H, m), 7.79-7.76 (3H, m), 7.66 (1H, t, J=7.5 Hz), 7.54-7.48 (2H, m), 7.03-6.95 (2H, m), 5.65 (1H, q, J=6.2 Hz), 2.51 (1H, s), 1.35 (3H, d, J=6.3 Hz); m/z (ES+) 407 [(M-OH)+].

Workup

  1. customdegassed
  2. customThe cooled reaction mixture
  3. extractionextracted with diethyl ether (x4)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography on silica
  8. washeluting with 5%
  9. washA second column, eluting with 60% diethyl ether/isohexane

Sources & evidence

ORD record
ord-e30a3a2243824c7abfb49235fe7dd579
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Linked notes

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