Sodium hydride → 3-Butoxy-4-(pyrrolidin-3-yloxy)-[1,2,5]thiadiazole

HRID 399650

Reaction equation

HRID 399650 reaction equation
[H-].[Na+].C(NC([N:10]1[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11]1)=O)(C)(C)C.[CH2:16]([O:20][C:21]1[C:25](S(C)(=O)=O)=[N:24][S:23][N:22]=1)[CH2:17][CH2:18][CH3:19]>C1COCC1>[CH2:16]([O:20][C:21]1[C:25]([O:15][CH:12]2[CH2:13][CH2:14][NH:10][CH2:11]2)=[N:24][S:23][N:22]=1)[CH2:17][CH2:18][CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 196002891-t-Butylcarbamoyl-3-hydroxypyrrolidineHCID 196003073-Butyloxy-4-methanesulfonyl-1,2,5-thiadiazole

Product 1

HCID 108002873-Butoxy-4-(pyrrolidin-3-yloxy)-[1,2,5]thiadiazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A suspension of NaH (0.066 g, 0.0028 mol) in THF (25 mL) was treated with 1-t-butylcarbamoyl-3-hydroxypyrrolidine (Ref. Syn. Commun. 15, 587.) (0.5 g, 0.0027 mol) and the reaction warmed to 50° C. for 30 min. After cooling to ambient temperature, 3-butyloxy-4-methanesulfonyl-1,2,5-thiadiazole (0.55 g, 0.0027 mol) in THF (5 mL) was added and the reaction heated to reflux for 2.5 h. The solvent was evaporated, the residue treated with ice-water, and the mixture extracted with ether. The extracts were washed with brine, dried, and the solvent evaporated. The residue was dissolved in ether (50 mL) and treated with a slow stream of HCl for 5 min. After stirring overnight, the reaction was extracted with cold water. The aqueous was washed with ether, made basic, and extracted with EtOAc. The extracts were washed with brine, dried, and the solvent evaporated to give a clear oil. The HCl salt (0.42 g) crystallized from EtOAc, m.p. 127°-128° C. (Compound 27).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. temperaturethe reaction heated
  3. temperatureto reflux for 2.5 h
  4. customThe solvent was evaporated
  5. additionthe residue treated with ice-water
  6. extractionthe mixture extracted with ether
  7. washThe extracts were washed with brine
  8. customdried
  9. customthe solvent evaporated
  10. dissolutionThe residue was dissolved in ether (50 mL)
  11. additiontreated with a slow stream of HCl for 5 min
  12. extractionthe reaction was extracted with cold water
  13. washThe aqueous was washed with ether
  14. extractionextracted with EtOAc
  15. washThe extracts were washed with brine
  16. customdried
  17. customthe solvent evaporated
  18. customto give a clear oil
  19. customThe HCl salt (0.42 g) crystallized from EtOAc, m.p. 127°-128° C. (Compound 27)

Sources & evidence

ORD record
ord-514ed3bcea264fbc82b5dd2fb8c1e754
Source dataset
uspto-grants-1998_10
Patent number
US05821370

Linked notes

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