Hydrochloric Acid → HCID 131724157, compound

HRID 478406Notes

Reaction equation

HRID 478406 reaction equation
C([N:8]1[CH2:13][CH2:12][C@H:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])[CH2:16][CH2:15]2)[C@H:10]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:9]1)C1C=CC=CC=1.Cl.[H][H].C(N(CC)CC)C.[F:42][C:43]([F:58])([F:57])[C:44]1[CH:45]=[C:46]([CH:50]=[C:51]([C:53]([F:56])([F:55])[F:54])[CH:52]=1)[C:47](Cl)=[O:48]>CO.[Pd].O>[F:42][C:43]([F:58])([F:57])[C:44]1[CH:45]=[C:46]([CH:50]=[C:51]([C:53]([F:56])([F:55])[F:54])[CH:52]=1)[C:47]([N:8]1[CH2:13][CH2:12][C@H:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20](=[O:25])[C:21]([F:24])([F:22])[F:23])[CH2:16][CH2:15]2)[C@H:10]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:9]1)=[O:48]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 131724156HCID 131724156, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 131724157HCID 131724157, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Rac-cis-1-[4-(1-benzyl-3-phenyl-piperidin-4-yl)-piperazin-1-yl]-2,2,2-trifluoro-ethanone (4.60 g, 10.7 mmol) was dissolved in methanol (200 mL) and concentrated hydrochloric acid (1.0 mL) and palladium on charcoal (10%, 700 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 (100 mL) and triethylamine (7.25 mL, 51.7 mmol) and 3,5-bistrifluoromethyl-benzoyl chloride (2.06 mL, 11.4 mmol) were added. The reaction mixture was stirred at room temperature overnight and than diluted with 100 mL water. The organic phase was separated and the aqueous layer was extracted twice with 100 mL dichloromethane. Organic phases were pooled, dried with magnesium sulfate and evaporated. Flash chromatography on silica gel with hexane/ethyl acetate/triethyl amine 90:10:1 gave the desired product (5.26 g, 87%) as a white foam, MS: m/e=582.0 (M+H+).

Workup

  1. filtrationwas filtered
  2. customthe solvent was evaporated
  3. dissolutionThe crude intermediate was dissolved in dichloromethane (100 mL)
  4. customThe organic phase was separated
  5. extractionthe aqueous layer was extracted twice with 100 mL dichloromethane
  6. dry with materialdried with magnesium sulfate
  7. customevaporated

Sources & evidence

ORD record
ord-981f81f8a1954c14af812e41ffb26419
Source dataset
uspto-grants-2003_11
Patent number
US06642226B2

Reaction notes

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