Ammonium formate → 4-[(1-Azetidin-3-ylpiperidin-4-yl)carbonyl]morpholine

HRID 426092Notes

Reaction equation

HRID 426092 reaction equation
C1(C(C2C=CC=CC=2)[N:8]2[CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][CH:15]([C:18]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[O:19])[CH2:14][CH2:13]3)[CH2:9]2)C=CC=CC=1.C([O-])=O.[NH4+]>C(O)C.[OH-].[OH-].[Pd+2]>[NH:8]1[CH2:9][CH:10]([N:12]2[CH2:17][CH2:16][CH:15]([C:18]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)=[O:19])[CH2:14][CH2:13]2)[CH2:11]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 236589584-({1-[1-(Diphenylmethyl)azetidin-3-yl]piperidin-4-yl}carbonyl)morpholine

Product 1

HCID 236589574-[(1-Azetidin-3-ylpiperidin-4-yl)carbonyl]morpholineYield 43.4%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

4-({1-[1-(Diphenylmethyl)azetidin-3-yl]piperidin-4-yl}carbonyl)morpholine (0.44 g, 1.0 mmol) was dissolved in ethanol and to the resultant solution was added palladium hydroxide on carbon (0.15 g) and ammonium formate (0.27 g, 4.2 mmol). The reaction mixture was heated for 2 min at 120° C. using microwave single node heating. The catalyst was filtered off by means of a phase separator and the filter cake washed with ethanol. The solvent was removed by evaporation and the residue was dissolved in methanol (1 mL) and THF (10 mL). The solution was loaded on a cation exchange sorbent (Isolute® SCX-2; 10 g). The column washed with THF and the product was then eluted with ammonia saturated methanol. The solvent of the collected fractions was removed by evaporation and there was obtained 0.11 g of the title compound as colourless oil. 1H NMR (500 MHz, CD3OD): 1.7-1.8 (m, 4H), 1.9-2.0 (m, 2H), 2.6-2.9 (m, 4H), 3.3-3.4 (m, 1H), 3.5-3.7 (m, 8H), 3.8-4.0 (m, 3H); LCMS: m/z 254 (M+1)+.

Workup

  1. temperatureheating
  2. filtrationThe catalyst was filtered off by means of a phase separator
  3. washthe filter cake washed with ethanol
  4. customThe solvent was removed by evaporation
  5. dissolutionthe residue was dissolved in methanol (1 mL)
  6. washThe column washed with THF
  7. washthe product was then eluted with ammonia saturated methanol
  8. customThe solvent of the collected fractions was removed by evaporation

Sources & evidence

ORD record
ord-d873ece4845a454183594df8097b4145
Source dataset
uspto-grants-2012_01
Patent number
US08106208B2

Reaction notes

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