Sodium hydride → 3-Butyloxy-4-(3-azetidinyloxy)-1,2,5-thiadiazole

HRID 399664

Reaction equation

HRID 399664 reaction equation
[H-].[Na+].C(NC([N:10]1[CH2:13][CH:12]([OH:14])[CH2:11]1)=O)(C)(C)C.[CH2:15]([O:19][C:20]1[C:24](S(C)(=O)=O)=[N:23][S:22][N:21]=1)[CH2:16][CH2:17][CH3:18]>C1COCC1>[CH2:15]([O:19][C:20]1[C:24]([O:14][CH:12]2[CH2:11][NH:10][CH2:13]2)=[N:23][S:22][N:21]=1)[CH2:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 196003073-Butyloxy-4-methanesulfonyl-1,2,5-thiadiazoleHCID 196003721-t-Butylcarbamoyl-3-hydroxyazetidine

Product 1

HCID 106570393-Butyloxy-4-(3-azetidinyloxy)-1,2,5-thiadiazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of NaH (0.24 g, 0.006 mol) in THF (30 mL) was treated with 1-t-butylcarbamoyl-3-hydroxyazetidine (1.1 g, 0.006 mol), the reaction stirred 1 h, followed by addition of 3-butyloxy-4-methanesulfonyl-1,2,5-thiadiazole (1.0 g, 0.0042 mol) in THF (5 mL). The reaction was heated to reflux for 4 h, the solvent evaporated, the residue treated with ice-water, and the mixture extracted with EtOAc. The extracts were dried and treated with a slow stream of HCl for 3 min. After 0.5 h, the solvent was evaporated, the residue treated with ice-water, and the solution extracted with ether. The aqueous phase was made basic, extracted with EtOAc, the extracts washed with brine, dried, and the solvent evaporated to give a clear oil. The HCl salt (0.77 g) crystallized from 2-propanol, m.p. 167°-168.5° C. (Compound 50).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 4 h
  3. customthe solvent evaporated
  4. additionthe residue treated with ice-water
  5. extractionthe mixture extracted with EtOAc
  6. customThe extracts were dried
  7. additiontreated with a slow stream of HCl for 3 min
  8. waitAfter 0.5 h
  9. customthe solvent was evaporated
  10. additionthe residue treated with ice-water
  11. extractionthe solution extracted with ether
  12. extractionextracted with EtOAc
  13. washthe extracts washed with brine
  14. customdried
  15. customthe solvent evaporated
  16. customto give a clear oil
  17. customThe HCl salt (0.77 g) crystallized from 2-propanol, m.p. 167°-168.5° C. (Compound 50)

Sources & evidence

ORD record
ord-ad8002a02ae24a2e9bb877211a8beaf3
Source dataset
uspto-grants-1998_10
Patent number
US05821371

Linked notes

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