Dimethylformamide → 4-[2-[3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxy]-4-phenyl-5-oxazolyl]benzenesulfonamide

HRID 890871Notes

Reaction equation

HRID 890871 reaction equation
Cl[C:2]1[O:3][C:4]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:6]=1.CN(C=O)C.C(=O)([O-])[O-].[K+].[K+].[F:34][C:35]1[CH:36]=[C:37]([C:42]2([O:48][CH3:49])[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)[CH:38]=[C:39]([OH:41])[CH:40]=1>C(OCC)(=O)C>[F:34][C:35]1[CH:40]=[C:39]([CH:38]=[C:37]([C:42]2([O:48][CH3:49])[CH2:43][CH2:44][O:45][CH2:46][CH2:47]2)[CH:36]=1)[O:41][C:2]1[O:3][C:4]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:6]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 117362763-Fluoro-5-(4-methoxytetrahydro-2H-pyran-4-yl)phenolHCID 222460994-(2-Chloro-4-phenyl-5-oxazolyl)benzenesulfonamide

Product 1

HCID 129861264-[2-[3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxy]-4-phenyl-5-oxazolyl]benzenesulfonamideYield 35%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-[2-Chloro-4-phenyl-5-oxazolyl]benzenesulfonamide from Step 3 (0.74 g, 2.2 mmol), N,N′-dimethylformamide (DMF) (20 mL), potassium carbonate (0.61 g, 4.4 mmol), and 4-(3-fluoro-5-hydroxyphenyl)-4-methoxy-3,4,5,6-tetrahydro-2H-pyran [prepared as described by G. C. Crawley, et al, J. Med. Chem., 35, 2600–2609 (1992)] (0.75 g, 7.5 mmol) were stirred at room temperature for 16.0 hours. The solution was diluted with ethyl acetate (100 mL), washed with 1N HCl, brine and water, dried over MgSO4 and concentrated. The residue was dissolved in ethyl acetate/hexanes (1:1) and filtered through silica. The eluant was concentrated and the residue was recrystallized from ethyl acetate/hexanes to afford 4-[2-[3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxy]-4-phenyl-5-oxazolyl]benzenesulfonamide as a white solid (0.4 g, 35%): mp 159–161° C. 1H NMR (CDCl3) 300 MHz δ 7.9 (d, J=8.7 Hz, 2H) 7.72 (d, J=8.7 Hz, 2H) 7.6 (m, 2H) 7.4 (m, 3H) 7.24–7.30 (m, 2H) 7.0–7.1 (dt, J=9.5 Hz and J=1.8 Hz, 1H) 4.85 (bs, 2H) 3.85 (dd, J=9.9 Hz and J=1.8 Hz, 4H) 3.05 (s, 3H) 2.0 (m, 4H). Anal. Calc'd. for C27H25N2O6SF: C, 61.82; H, 4.80; N, 5.34. Found: C, 61.77; H, 4.82; N, 4.31.

Workup

  1. washwashed with 1N HCl, brine and water
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in ethyl acetate/hexanes (1:1)
  5. filtrationfiltered through silica
  6. concentrationThe eluant was concentrated
  7. customthe residue was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-75536377b85d46678a99e5d428545984
Source dataset
uspto-grants-2006_02
Patent number
US06998415B2

Reaction notes

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