Triethylamine → HCID 131724192, compound

HRID 478443Notes

Reaction equation

HRID 478443 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]3[CH2:23][CH2:22][N:21]([C@H:24]4[CH2:29][CH2:28][N:27](CC5C=CC=CC=5)[CH2:26][C@H:25]4[C:37]4[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=4)[CH2:20][CH2:19]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.ClC(OC(Cl)=O)C.C(N(CC)CC)C.[F:58][C:59]([F:74])([F:73])[C:60]1[CH:61]=[C:62]([CH:66]=[C:67]([C:69]([F:72])([F:71])[F:70])[CH:68]=1)[C:63](Cl)=[O:64]>C1(C)C=CC=CC=1.O.CO>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([N:18]3[CH2:19][CH2:20][N:21]([C@H:24]4[CH2:29][CH2:28][N:27]([C:63](=[O:64])[C:62]5[CH:61]=[C:60]([C:59]([F:74])([F:73])[F:58])[CH:68]=[C:67]([C:69]([F:72])([F:71])[F:70])[CH:66]=5)[CH2:26][C@H:25]4[C:37]4[CH:38]=[CH:39][C:40]([Cl:43])=[CH:41][CH:42]=4)[CH2:22][CH2:23]3)=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 5213051-Chloroethyl chloroformateHCID 131724191HCID 131724191, compound

Product 1

HCID 131724192HCID 131724192, compoundYield 87.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Rac-cis-4-[1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-piperazine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (1.68 g, 2.84 mmol) was dissolved in toluene (60 mL) and 1-chloroethyl-chloroformate (0.348 mL, 3.13 mmol) were added. The reaction mixture was refluxed overnight. Methanol (55 mL) was added and reflux was continued for 4 h. The solvents were evaporated. The crude intermediate was dissolved in dichloromethane (50 mL) and triethylamine (1.99 mL, 14.2 mmol) and 3,5-bistrifluoromethyl-benzoyl chloride (0.643 mL, 3.55 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 cyclohexane/ethyl acetate 1:1 gave rac-cis-4-[1-(3,5-bis-trifluoromethyl-benzoyl)-3-(4-chloro-phenyl)-piperidin-4-yl]-piperazine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (1.84 g, 87%) as an off-white solid, MS: m/e=742.3 (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 (50 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-2cdc4bede9c7459187369cbcc276a469
Source dataset
uspto-grants-2003_11
Patent number
US06642226B2

Reaction notes

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