Lithium Hexamethyldisilazide → 5-Bromo-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920269Notes

Reaction equation

HRID 920269 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][O:12][C:13]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:14]=1[CH2:15][NH:16][C:17]1[S:21][N:20]=[CH:19][N:18]=1.[Br:28][C:29]1[C:30]([S:39](Cl)(=[O:41])=[O:40])=[CH:31][C:32]2[O:36][C:35](=[O:37])[NH:34][C:33]=2[CH:38]=1>C1COCC1>[Br:28][C:29]1[C:30]([S:39]([N:16]([CH2:15][C:14]2[CH:22]=[CH:23][C:24]([O:26][CH3:27])=[CH:25][C:13]=2[O:12][CH3:11])[C:17]2[S:21][N:20]=[CH:19][N:18]=2)(=[O:40])=[O:41])=[CH:31][C:32]2[O:36][C:35](=[O:37])[NH:34][C:33]=2[CH:38]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 126110465-Bromo-2-oxo-2,3-dihydro-1,3-benzoxazole-6-sulfonyl chlorideHCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 895337855-Bromo-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Added LHMDS (1603 μl, 1.603 mmol, 1M in THF) to 1-3 (422 mg, 1.679 mmol) in THF (1908 μl) at −78° C. Removed cooling bath and stirred at RT for 30 min. Cooled back to −78 C and slowly added the 35-2 (159 mg, 0.509 mmol) in THF (636 μl). The resulting reaction mixture was allowed to slowly warm to RT while remaining in bath. After 2 h, quenched with 5 mL saturated NH4Cl and diluted with 10 mL EtOAc. Separated layers, back-extracted aqueous with 3×5 mL EtOAc. Dried over Na2SO4, filtered, concentrated to give a clear, orange oil. Purified by normal-phase HPLC (40 g ISCO column, 0-50% EtOAc:Hex) to give 35-3 as a white solid.

Workup

  1. customRemoved
  2. temperaturecooling bath
  3. temperatureCooled back to −78 C
  4. customThe resulting reaction mixture
  5. temperatureto slowly warm to RT
  6. customwhile remaining in bath
  7. waitAfter 2 h
  8. customquenched with 5 mL saturated NH4Cl
  9. additiondiluted with 10 mL EtOAc
  10. extractionSeparated layers, back-extracted aqueous with 3×5 mL EtOAc
  11. dry with materialDried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto give a clear, orange oil
  15. customPurified by normal-phase HPLC (40 g ISCO column, 0-50% EtOAc:Hex)

Sources & evidence

ORD record
ord-20d7ee0c723346a5b459544c0b1c8c4f
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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