Sodium Carbonate → (1S)-1-(2-{[6-(2-Fluorophenyl)-2-naphthyl]sulfonyl}phenyl)ethanol

HRID 735336Notes

Reaction equation

HRID 735336 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C@@H:21]([OH:23])[CH3:22])(=[O:14])=[O:13])[CH:6]=[CH:5]2.[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C@@H:21]([OH:23])[CH3:22])(=[O:13])=[O:14])[CH:6]=[CH:5]2

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 80271Tri-o-tolylphosphineHCID 27343542-Fluorophenylboronic acidHCID 68899466(1S)-1-{2-[(6-bromo-2-naphthyl)sulfonyl]phenyl}ethanol

Product 1

HCID 68902350(1S)-1-(2-{[6-(2-Fluorophenyl)-2-naphthyl]sulfonyl}phenyl)ethanolYield 81.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (1S)-1-{2-[(6-bromo-2-naphthyl)sulfonyl]phenyl}ethanol [Example 10 Step 2] (102 mg, 0.26 mmol), 2-fluorophenylboronic acid (75 mg, 0.53 mmol), palladium(II) acetate (3 mg, 0.013 mmol), tri(o-tolyl)phosphine (9 mg, 0.028 mmol), sodium carbonate (83 mg, 0.787 mmol) and water (0.5 mL) in 1,2-dimethoxyethane (3 mL) was degassed and stirred at 80° C. (oil bath temperature) under nitrogen for 16 hours. The cooled reaction mixture was diluted with ethyl acetate and filtered. The filtrate was evaporated and the residue purified by flash chromatography, eluting with 60-75% diethyl ether/isohexane, to afford the title compound as a foam (86 mg, 81%). 1H NMR (500 MHz, CDCl3) δ 8.56 (1H, s), 8.17 (1H, dd, J 1.0, 8.0 Hz), 8.06 (2H, m), 7.98 (1H, d, J 8.6 Hz), 7.83 (1H, m), 7.77 (2H, m), 7.66 (1H, t, J 7.5 Hz), 7.54 (1H, dt, J 1.6, 7.7 Hz), 7.49 (1H, t, J 7.7 Hz), 7.42-7.38 (1H, m), 7.28 (1H, m), 7.21 (1H, m), 5.68-5.62 (1H, m), 2.51 (1H, d, J 3.2 Hz), 1.36 (3H, d, J 6.3 Hz); m/z (ES+) 389 [(M-OH)+].

Workup

  1. customwas degassed
  2. customThe cooled reaction mixture
  3. filtrationfiltered
  4. customThe filtrate was evaporated
  5. customthe residue purified by flash chromatography
  6. washeluting with 60-75% diethyl ether/isohexane

Sources & evidence

ORD record
ord-35006b8da5e74fb598801afcb0e47a04
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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