Morpholine → HCID 131724171, compound

HRID 478420Notes

Reaction equation

HRID 478420 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C([BH3-])#N.[Na+]>C(O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C@H:10]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[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 18001162HCID 18001162, compound

Product 1

HCID 131724171HCID 131724171, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a mixture of 1-benzyl-3-(4-chloro-phenyl)-piperidin-4-one (1.0 g, 3.34 mmol) and morpholine (1.16 mL, 13.3 mmol) was added tetraisopropyl-orthotitanate (3.95 mL, 13.3 mmol) at room temperature. After stirring at room temperature overnight the reaction mixture was diluted with ethanol (30.0 mL) and sodium cyanoborohydride (930 mg, 13.3 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 hexane/ethyl acetate/triethylamine 40:10:1 to give rac-cis-4-[1-benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-morpholine (650 mg, 52%) as a yellow solid, MS: m/e=371.3 (M+H+).

Workup

  1. additionwas added tetraisopropyl-orthotitanate (3.95 mL, 13.3 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 hexane/ethyl acetate/triethylamine 40:10:1

Sources & evidence

ORD record
ord-68d99ac7741d458e9fc64bc70f60b091
Source dataset
uspto-grants-2003_11
Patent number
US06642226B2

Reaction notes

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