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

HRID 1161115Notes

Reaction equation

HRID 1161115 reaction equation
C([Mg]Cl)(C)C.I[C:7]1[CH:35]=[CH:34][C:10]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([O:21][Si](C)(C)C)=[CH2:20])=[C:15]([O:26][Si](C)(C)C)[C:14]=2[CH2:31][CH2:32][CH3:33])=[CH:9][CH:8]=1.[H-].[Na+].[O:38]=[C:39]1[O:43][N:42]=[C:41]([C:44]2[CH:45]=[C:46]([CH:49]=[CH:50][CH:51]=2)[CH:47]=[O:48])[NH:40]1>O1CCCC1>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([O:12][CH2:11][C:10]2[CH:34]=[CH:35][C:7]([CH:47]([OH:48])[C:46]3[CH:45]=[C:44]([C:41]4[NH:40][C:39](=[O:38])[O:43][N:42]=4)[CH:51]=[CH:50][CH:49]=3)=[CH:8][CH:9]=2)=[C:14]([CH2:31][CH2:32][CH3:33])[C:15]=1[OH:26])(=[O:21])[CH3:20]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 66699606HCID 66699606, compoundHCID 1360829193-(5-Oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-benzaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 1361597193-(3-{[4-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-hydroxy-methyl}-phenyl)-4H-[1,2,4]oxadiazol-5-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add isopropyl magnesium chloride (2M solution in tetrahydrofuran, 0.496 ml, 0.992 mmol) to a solution of 1-(4-iodo-benzyloxy)-2-propyl-3-trimethylsilanyloxy-4-(1-trimethylsilanyloxy-vinyl)-benzene (500 mg, 0.901 mmol) in tetrahydrofuran (0.1M) at 0° C. After 15 minutes, warm to room temperature. After 1 hour, cool to −78° C. Add sodium hydride (60% dispersion, 24 mg, 0.992 mmol) to a solution of 3-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-benzaldehyde (189 mg, 0.992 mmol) in tetrahydrofuran (0.1M). 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 (3 mL). Pour the reaction into brine and extract with 25% isopropyl alcohol:75% dichloromethane. Combine 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 off white solid (110 mg, 26%): 1H NMR (DMSO-d6) δ 0.86 (t, 3H), 1.47 (sextet, 2H), 2.56 (m, 5H), 5.21 (s, 2H), 5.79 (d, 1H), 6.11 (d, 1H), 6.70 (d, 1H), 7.41 (q, 4H), 7.51 (t, 1H), 7.63 (t, 2H), 7.78 (d, 1H), 7.90 (s, 1H), 12.83 (s, 1H), 12.97 (bs, 1H); MS (esi negative) m/z (rel intensity) 473 (100).

Workup

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

Sources & evidence

ORD record
ord-7b73104c0c1d4e74a04f3fe78baf0ee2
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

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