Triethylamine → HCID 131724172, compound

HRID 478421Notes

Reaction equation

HRID 478421 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][C:23]([Cl:26])=[CH:22][CH:21]=2)[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)=O)C.C(N(CC)CC)C.[F:41][C:42]([F:57])([F:56])[C:43]1[CH:44]=[C:45]([CH:49]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:51]=1)[C:46](Cl)=[O:47]>ClCCl.O.CO>[F:41][C:42]([F:57])([F:56])[C:43]1[CH:44]=[C:45]([C:46]([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][C:23]([Cl:26])=[CH:22][CH:21]=3)[CH2:9]2)=[O:47])[CH:49]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:51]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 5213051-Chloroethyl chloroformateHCID 131724171HCID 131724171, compound

Product 1

HCID 131724172HCID 131724172, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Rac-cis-4-[1-benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-morpholine (650 mg, 1.75 mmol) was dissolved in dichloromethane (15 mL) and 1-chloroethyl-chloroformate (0.575 mL, 5.27 mmol) were added at 0° C. The reaction mixture was refluxed overnight. Methanol (15 mL) was added and reflux was continued for 3 h. The solvents were evaporated. The crude intermediate was dissolved in dichloromethane (30 mL) and triethylamine (1.22 mL, 8.75 mmol) and 3,5-bistrifluoromethyl-benzoyl chloride (0.35 mL, 1.93 mmol) were added. The reaction mixture was stirred at room temperature overnight and than diluted with 50 mL water. The organic phase was separated and the aqueous layer was extracted twice with 50 mL dichloromethane. Organic phases were pooled, dried with magnesium sulfate and evaporated. Flash chromatography on silica gel with hexane/ethyl acetate/triethylamine 20:10.1 gave the desired product (820 mg, 90%) as a yellow solid, MS: m/e=521.1 (M+H+).

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. temperaturereflux
  3. customThe solvents were evaporated
  4. dissolutionThe crude intermediate was dissolved in dichloromethane (30 mL)
  5. customThe organic phase was separated
  6. extractionthe aqueous layer was extracted twice with 50 mL dichloromethane
  7. dry with materialdried with magnesium sulfate
  8. customevaporated

Sources & evidence

ORD record
ord-bfcbf3edabc447bd8668c5199aa7fc8b
Source dataset
uspto-grants-2003_11
Patent number
US06642226B2

Reaction notes

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