Ammonia → 1-(3,5-Bis-trifluoromethyl-benzoyl)-4-(3-chloro-phenylamino)-piperidine-4-carbonitrile

HRID 1018642Notes

Reaction equation

HRID 1018642 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7].[Cl:24][C:25]1[CH:26]=[C:27]([CH:29]=[CH:30][CH:31]=1)[NH2:28].C[Si]([C:36]#[N:37])(C)C.N>C(O)(=O)C>[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[C:6]([N:8]1[CH2:13][CH2:12][C:11]([NH:28][C:27]2[CH:29]=[CH:30][CH:31]=[C:25]([Cl:24])[CH:26]=2)([C:36]#[N:37])[CH2:10][CH2:9]1)=[O:7]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 79323-ChloroanilineHCID 82115Trimethylsilyl cyanideHCID 112099631-(3,5-Bis(trifluoromethyl)benzoyl)piperidin-4-one

Product 1

HCID 184016341-(3,5-Bis-trifluoromethyl-benzoyl)-4-(3-chloro-phenylamino)-piperidine-4-carbonitrileYield 74.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 1-(3,5-bis-trifluoromethyl-benzoyl)-piperidin-4-one (5.1 g, 15 mmol) in acetic acid (20 mL) were added with cooling 3-chloroaniline (1.7 mL, 16.5 mmol) and trimethylsilylcyanide (1.9 mL, 15 mmol) so that the temperature did not rise above 20° C. The suspension was stirred for 6 h at room temperature. The reaction mixture was than added to ice-water (350 mL), ammonia (55 mL, 25%) was added to the mixture which was stirred for 15 min. After that the mixture was extracted with dichloromethane, the organic phases were pooled, washed with brine and dried with MgSO4. The solvent was evaporated and the residue crystallized from ethylacetate to yield the desired product (5.3 g, 74%), m.p. 205-207° C. and MS: m/e=476.1 (M+H+).

Workup

  1. customdid not rise above 20° C
  2. additionwas added to the mixture which
  3. stirringwas stirred for 15 min
  4. extractionAfter that the mixture was extracted with dichloromethane
  5. washwashed with brine
  6. dry with materialdried with MgSO4
  7. customThe solvent was evaporated
  8. customthe residue crystallized from ethylacetate

Sources & evidence

ORD record
ord-0cc7c83b72344655b74f70b1e01513f1
Source dataset
uspto-grants-2002_11
Patent number
US06482829B2

Reaction notes

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