Morpholine → Rac-cis-4-(1-benzyl-3-phenyl-piperidin-4-yl)-morpholine

HRID 478398Notes

Reaction equation

HRID 478398 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C([BH3-])#N.[Na+]>C(O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C@H:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 5003444Sodium cyanoborohydrideHCID 118179561-Benzyl-3-phenylpiperidin-4-one

Product 1

HCID 131724148Rac-cis-4-(1-benzyl-3-phenyl-piperidin-4-yl)-morpholineYield 54.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a mixture of 1-benzyl-3-phenyl-piperidin-4-one (2.07 g, 7.78 mmol) and morpholine (678 mg, 7.78 mmol) was added tetraisopropyl-orthotitanate (2.97 mL, 9.73 mmol) at room temperature. After stirring at room temperature overnight the reaction mixture was diluted with ethanol (8.0 mL) and sodium cyanoborohydride (369 mg, 5.37 mmol) was added. The reaction mixture was stirred at room temperature for 24 h and was diluted with water (2.0 mL). The inorganic precipitate was filtered off and washed with ethanol. The filtrate was evaporated and purified by flash chromatography on silica gel with toluene/ethyl acetate 6:1 to give rac-cis-4-(1-benzyl-3-phenyl-piperidin-4-yl)-morpholine (1.42 g, 54%) as a yellow solid, MS: m/e=337.3 (M+H+).

Workup

  1. additionwas added tetraisopropyl-orthotitanate (2.97 mL, 9.73 mmol) at room temperature
  2. additionwas added
  3. stirringThe reaction mixture was stirred at room temperature for 24 h
  4. filtrationThe inorganic precipitate was filtered off
  5. washwashed with ethanol
  6. customThe filtrate was evaporated
  7. custompurified by flash chromatography on silica gel with toluene/ethyl acetate 6:1

Sources & evidence

ORD record
ord-2e969a9dfac24666a95fabd8ef61fc44
Source dataset
uspto-grants-2003_11
Patent number
US06642226B2

Reaction notes

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