Sodium hydride → 3-(3-{[3-(4-acetyl-2-chloro-3-hydroxy-phenoxymethyl)-phenyl]-hydroxy-methyl}-phenyl)-4H-[1,2,4]oxadiazol-5-one

HRID 1818556Notes

Reaction equation

HRID 1818556 reaction equation
C([Mg]Cl)(C)C.[Cl:6][C:7]1[C:12]([O:13][Si](C)(C)C)=[C:11]([C:18]([O:20][Si](C)(C)C)=[CH2:19])[CH:10]=[CH:9][C:8]=1[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29](I)[CH:28]=1.[H-].[Na+].[O:36]=[C:37]1[O:41][N:40]=[C:39]([C:42]2[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=2)[CH:45]=[O:46])[NH:38]1>O1CCCC1>[C:18]([C:11]1[CH:10]=[CH:9][C:8]([O:25][CH2:26][C:27]2[CH:28]=[C:29]([CH:45]([OH:46])[C:44]3[CH:43]=[C:42]([C:39]4[NH:38][C:37](=[O:36])[O:41][N:40]=4)[CH:49]=[CH:48][CH:47]=3)[CH:30]=[CH:31][CH:32]=2)=[C:7]([Cl:6])[C:12]=1[OH:13])(=[O:20])[CH3:19]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 666995542-Chloro-1-(3-iodo-benzyloxy)-3-trimethylsilanyloxy-4-(1-trimethylsilanyloxy-vinyl)-benzeneHCID 1360829193-(5-Oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-benzaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 1361597233-(3-{[3-(4-acetyl-2-chloro-3-hydroxy-phenoxymethyl)-phenyl]-hydroxy-methyl}-phenyl)-4H-[1,2,4]oxadiazol-5-oneYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Add isopropyl magnesium chloride (2M solution in tetrahydrofuran, 1.01 mL, 2.02 mmol) to a solution of 2-chloro-1-(3-iodo-benzyloxy)-3-trimethylsilanyloxy-4-(1-trimethylsilanyloxy-vinyl)-benzene (1.00 g, 1.83 mmol) in tetrahydrofuran (0.1M) chilled to 0° C. After 15 minutes, warm to room temperature. After 1 hour, cool to −78° C. Add sodium hydride (60% dispersion, 80 mg, 2.01 mmol) to a solution of 3-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-benzaldehyde (348 mg, 1.83 mmol) in tetrahydrofuran (0.1 M). Sonicate the solution for 5 minutes then add it via syringe to the gringard reagent. After 30 minutes, warm the reaction to room temperature. Quench with 10% aq hydrochloric acid. Pour the reaction into brine and extract with 25% isopropyl alcohol:75% dichloromethane. Combine the organic layers, dry with sodium sulfate, filter and concentrate under reduced pressure to give a residue. Purify the residue by flash chromatography eluting with ethyl acetate:hexanes:acetic acid (50%:50%:0.1%) to yield the title product as a white solid (120 mg, 14%): 1H NMR (DMSO-d6) δ 2.61 (s, 3H), 5.32 (s, 2H), 5.79 (d, 1H), 6.15 (d, 1H), 6.87 (d, 1H), 7.32-7.41 (m, 3H), 7.49 (m, 2H), 7.59 (dt, 1H), 7.64 (dt, 1H), 7.89-7.92 (m, 2H), 12.96 (bs, 1H), 13.13 (s, 1H); MS (esi negative) m/z (rel intensity) 465 (100).

Workup

  1. temperaturewarm to room temperature
  2. waitAfter 1 hour
  3. temperaturecool to −78° C
  4. customSonicate the solution for 5 minutes
  5. additionthen add it via syringe to the gringard reagent
  6. waitAfter 30 minutes
  7. temperaturewarm
  8. customthe reaction to room temperature
  9. customQuench with 10% aq hydrochloric acid
  10. additionPour
  11. customthe reaction into brine
  12. extractionextract with 25% isopropyl alcohol
  13. dry with materialdry with sodium sulfate
  14. filtrationfilter
  15. concentrationconcentrate under reduced pressure
  16. customto give a residue
  17. customPurify the residue by flash chromatography
  18. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-54436868404f4efe8b9c21babece562b
Source dataset
uspto-grants-2009_10
Patent number
US07598423B2

Reaction notes

Loading…