Sodium Sulfate → Tert-butyl 4-(1-(oxetan-3-yl)-piperidin-4-yl)-piperazine-1-carboxylate

HRID 919370Notes

Reaction equation

HRID 919370 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[O:20]1[CH2:23][C:22](=O)[CH2:21]1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.O.C(O)(=O)C>[O:20]1[CH2:23][CH:22]([N:17]2[CH2:18][CH2:19][CH:14]([N:11]3[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]3)[CH2:15][CH2:16]2)[CH2:21]1

Participants

8

Reactant 4

HCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 17750356tert-Butyl 4-(piperidin-4-yl)piperazine-1-carboxylate

Product 1

HCID 90421509Tert-butyl 4-(1-(oxetan-3-yl)-piperidin-4-yl)-piperazine-1-carboxylateYield 26.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

In a 100 ml round-bottom flask 2 g (7.42 mmol) of 1-boc-4-(piperidin-4-yl)-piperazine and 1.07 g (14.85 mmol) of 3-oxetanone were dissolved in 30 ml of dichloromethane. 3.16 g (22.27 mmol) of sodium sulfate were added and the reaction was stirred for 10 min. Subsequently, 2.203 g (10.39 mmol) of sodium triacetoxyborohydride were added and the reaction was stirred for 5 min. pH was adjusted to 5-6 with acetic acid and the reaction was stirred over night. Then, 50 ml of water were added and the resulting two phases were separated. The organic phase was washed twice with water dried over MgSO4, filtered and evaporated. The resulting solid was digested in methyl-tert-butyl ether, filtered off, washed with 10 ml of methyl-tert-butyl ether and dried. Flash chromatography (silica gel/gradient from 0 to 20% methanol in dichloromethane) yielded 650 mg of the title compound as a yellowish solid.

Workup

  1. stirringthe reaction was stirred for 5 min.
  2. stirringthe reaction was stirred over night
  3. customthe resulting two phases were separated
  4. washThe organic phase was washed twice with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. filtrationfiltered off
  9. washwashed with 10 ml of methyl-tert-butyl ether
  10. customdried

Sources & evidence

ORD record
ord-eec7cf8e8f38404d8fbdf2030ed66a21
Source dataset
uspto-grants-2016_03
Patent number
US09273036B2

Reaction notes

Loading…