1,1'-Carbonyldiimidazole → N-[2-(3,4-Dichlorophenyl)-2-(4-hydroxy-4-phenyl-piperidino)ethyl]-N-methyl-3,5-bis(trifluoromethyl)phenylacetamide hydrochloride salt

HRID 1857659Notes

Reaction equation

HRID 1857659 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([CH2:13][C:14]([OH:16])=O)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:31][C:32]1[CH:33]=[C:34]([CH:39]([N:43]2[CH2:48][CH2:47][C:46]([OH:55])([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH2:45][CH2:44]2)[CH2:40][NH:41][CH3:42])[CH:35]=[CH:36][C:37]=1[Cl:38]>O1CCCC1>[ClH:31].[Cl:31][C:32]1[CH:33]=[C:34]([CH:39]([N:43]2[CH2:44][CH2:45][C:46]([OH:55])([C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=3)[CH2:47][CH2:48]2)[CH2:40][N:41]([CH3:42])[C:14](=[O:16])[CH2:13][C:5]2[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=[C:3]([C:2]([F:17])([F:18])[F:1])[CH:4]=2)[CH:35]=[CH:36][C:37]=1[Cl:38]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 1235873,5-Bis(trifluoromethyl)phenylacetic acidHCID 15434904HCID 15434904, compound

Product 1

HCID 22129658N-[2-(3,4-Dichlorophenyl)-2-(4-hydroxy-4-phenyl-piperidino)ethyl]-N-methyl-3,5-bis(trifluoromethyl)phenylacetamide hydrochloride saltYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
23 °C

Procedure

A solution of 3,5-bis(trifluoromethyl)phenylacetic acid (1.61 g) and 1,1'-carbonyldiimidazole (1.01 g) in tetrahydrofuran (15 mL) was stirred at reflux for 0.5 hours. The reaction was cooled to 23° C. and treated with a solution of N-[2-(3,4-dichlorophenyl)-2-(4-hydroxy-4-phenylpiperidino)ethyl]methylamine (2.24 g) in tetrahydrofuran (70 mL). The reaction was stirred at 23° C. for 18 hours. The reaction was evaporated to an oil, and the oil was partitioned between diethylether and 1N hydrochloric acid (100 mL). The organic layer was treated with etheral hydrochloric acid to produce the title compound as a white solid (950 mg); mp 230° C.; MS: m/z=633(M+1); NMR: 1.73 (m,2), 2.42 (m,1), 2.75 (m,1), 3.01 (s,4), 3.86 (m,4,), 4.43 (m,1), 4.85 (m,1), 5.34 (m,1), 7.34 (m,5), 7.73 (s 2), 7.87 (m,5), 8.06 (s,1), 11.36 (broad s,1). Analysis Calculated: C, 53.79; H, 4.36; N, 4.18; Found: C, 54.06; H, 4.48; N, 4.23.

Workup

  1. temperatureat reflux for 0.5 hours
  2. customThe reaction was evaporated to an oil
  3. customthe oil was partitioned between diethylether and 1N hydrochloric acid (100 mL)
  4. additionThe organic layer was treated with etheral hydrochloric acid

Sources & evidence

ORD record
ord-433bf4565c334c36a5591d7b8492ab3e
Source dataset
uspto-grants-2000_11
Patent number
US06147083

Reaction notes

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