Hydrochloric Acid → Rac-cis-(3,5-bis-trifluoromethyl-phenyl)-(4-morpholin-4-yl-3-phenyl-piperidin-1-yl)-methanone

HRID 478399Notes

Reaction equation

HRID 478399 reaction equation
C([N:8]1[CH2:13][CH2:12][C@H:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C@H:10]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9]1)C1C=CC=CC=1.Cl.[H][H].C(N(CC)CC)C.[F:36][C:37]([F:52])([F:51])[C:38]1[CH:39]=[C:40]([CH:44]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:46]=1)[C:41](Cl)=[O:42]>CO.[Pd].O>[F:36][C:37]([F:52])([F:51])[C:38]1[CH:39]=[C:40]([C:41]([N:8]2[CH2:13][CH2:12][C@H:11]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C@H:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:9]2)=[O:42])[CH:44]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:46]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 131724148Rac-cis-4-(1-benzyl-3-phenyl-piperidin-4-yl)-morpholineHCID 178418361HCID 178418361, compound

Product 1

HCID 131724149Rac-cis-(3,5-bis-trifluoromethyl-phenyl)-(4-morpholin-4-yl-3-phenyl-piperidin-1-yl)-methanoneYield 83.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Rac-cis-4-(1-benzyl-3-phenyl-piperidin-4-yl)-morpholine (1.3 g, 3.86 mmol) was dissolved in methanol (50 mL) and concentrated hydrochloric acid (0.2 mL) and palladium on charcoal (10%, 200 mg) were added. After stirring in a hydrogen atmosphere (1 bar) at room temperature overnight the mixture was filtered and the solvent was evaporated. The crude intermediate was dissolved in dichloromethane (20 mL) and triethylamine (2.69 mL, 19.3 mmol) and 3,5-bistrifluoromethyl-benzoyl chloride (0.91 mL, 5.02 mmol) were added. The reaction mixture was stirred at room temperature overnight and than diluted with 20 mL water. The organic phase was separated and the aqueous layer was extracted twice with 20 mL dichloromethane. Organic phases were pooled, dried with magnesium sulfate and evaporated. Flash chromatography on silica gel with hexane/ethyl acetate/triethyl amine 80:20:1 gave the desired product (1.57 g, 83%) as off-white crystalls, MS: m/e=487.3 (M+H+).

Workup

  1. filtrationwas filtered
  2. customthe solvent was evaporated
  3. dissolutionThe crude intermediate was dissolved in dichloromethane (20 mL)
  4. customThe organic phase was separated
  5. extractionthe aqueous layer was extracted twice with 20 mL dichloromethane
  6. dry with materialdried with magnesium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-a1d1f886c00a447eaea55aea4d7b4cea
Source dataset
uspto-grants-2003_11
Patent number
US06642226B2

Reaction notes

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