Tetrahydrofuran → 1-Boc-4-(5-methyl-1,3,4-oxadiazol-2-yl)piperidine

HRID 20265Notes

Reaction equation

HRID 20265 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH:16][NH2:17])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:18]1COC[CH2:19]1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[O:15][C:18]([CH3:19])=[N:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 22713165tert-Butyl 4-(hydrazinecarbonyl)piperidine-1-carboxylate

Product 1

HCID 210983641-Boc-4-(5-methyl-1,3,4-oxadiazol-2-yl)piperidineYield 81%

Conditions

Temperature
50 °C

Procedure

To a solution of 9.0 g of 4-Hydrazinocarbonyl-piperidine-1-carboxylic acid tert-butyl ester (see reference WO 9703986 A1 19970206) (37 mmoles, 1 eq.) in 40 ml of THF, were added 8.1 ml of (55.4 mmoles, 1.5 eq.). The reaction mixture was then stirred at 50° C. for 4 hours under nitrogen. The solvent was removed under reduced pressure, the residue dissolved in 40 ml of toluene, and 400 mg of para toluene sulfonic acid were added. The mixture was then heated at 100° C. under nitrogen for 18 hours, the volatiles were removed under reduced pressure and the residue was partitioned between methylene chloride and an aqueous solution of sodium bicarbonate. The organic phase was dried over magnesium sulfate and filtered. The volatiles were removed under reduced pressure and the residue was purified by column chromatography on silica gel using methylene chloride/methanol as eluant (98:2 v/v to 95:5 v/v) to afford 8.07 g of the title compound as a white solid (81%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue dissolved in 40 ml of toluene
  3. addition400 mg of para toluene sulfonic acid were added
  4. temperatureThe mixture was then heated at 100° C. under nitrogen for 18 hours
  5. customthe volatiles were removed under reduced pressure
  6. customthe residue was partitioned between methylene chloride
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. customThe volatiles were removed under reduced pressure
  10. customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-d8a63710e752497899807e50d32da16b
Source dataset
uspto-grants-2010_06
Patent number
US07745630B2

Reaction notes

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