2-Methylpentane → HCID 68902777, compound

HRID 735367Notes

Reaction equation

HRID 735367 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[CH:23]=[C:22]([S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C@@H:36]([OH:38])[CH3:37])(=[O:29])=[O:28])[CH:21]=[CH:20]3)O1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[Na+].[Na+].CCCC(C)C>COCCOC.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][CH:26]=2)[CH:23]=[C:22]([S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C@@H:36]([OH:38])[CH3:37])(=[O:29])=[O:28])[CH:21]=[CH:20]3)=[N:3][CH:4]=1

Participants

9

Reactant 5

HCID 78922-MethylpentaneHCID 10340Sodium CarbonateHCID 80271Tri-o-tolylphosphineHCID 27831712-Bromo-5-fluoropyridineHCID 68902058HCID 68902058, compound

Product 1

HCID 68902777HCID 68902777, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 2-bromo-5-fluoropyridine (38 mg, 0.22 mmol), (1S)-1-(2-{[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthyl]sulfonyl}phenyl)ethanol (96 mg, 0.22 mmol), palladium(II) acetate (2.6 mg, 11 μmol), tri(o-tolyl)phosphine (5.2 mg, 17 μmol) and sodium carbonate (51 mg, 0.48 mmol) in DME (2 mL) and water (0.3 mL) was degassed by bubbling nitrogen through for 5 minutes, then was heated at reflux under nitrogen for 3 hours. The slurry was filtered, and the filtrate was washed with saturated sodium hydrogen carbonate solution (10 mL), with saturated sodium chloride solution (10 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel, eluting with 40% ethyl acetate in isohexane, then further purified by preparative TLC on silica gel, eluting with 50% ethyl acetate in isohexane. The product was isolated as a colourless solid, which solidified upon trituration with isohexane (13 mg, 15%). 1H NMR (400 MHz, CDCl3): δ 8.61 (1H, d, J=2.7 Hz), 8.55 (1H, s), 8.48 (1H, s), 8.21 (2H, dd, J=8.7, 21.9 Hz), 8.06 (2H, dd, J=8.7, 22.5 Hz), 7.90 (1H, dd, J=4.1, 8.7 Hz), 7.77 (2H, d, J=7.6 Hz), 7.66 (1H, t, J=7.5 Hz), 7.57-7.49 (2H, m), 5.65 (1H, m), 2.48 (1H, s), 1.34 (3H, d, J=6.4 Hz). m/z (ES+) 408 [MH+].

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through for 5 minutes
  3. temperaturewas heated
  4. temperatureat reflux under nitrogen for 3 hours
  5. filtrationThe slurry was filtered
  6. washthe filtrate was washed with saturated sodium hydrogen carbonate solution (10 mL), with saturated sodium chloride solution (10 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica gel
  10. washeluting with 40% ethyl acetate in isohexane
  11. customfurther purified by preparative TLC on silica gel
  12. washeluting with 50% ethyl acetate in isohexane
  13. customThe product was isolated as a colourless solid, which

Sources & evidence

ORD record
ord-e1118bbe7ee74357ac322b30d8ec486e
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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