Ethyl 4-piperidinecarboxylate → HCID 86626852, compound

HRID 604103Notes

Reaction equation

HRID 604103 reaction equation
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1)[CH2:6][N:7]([C:28]1[N:33]=[CH:32][C:31](Br)=[CH:30][N:29]=1)[CH:8]([C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1[N:20]([CH2:24][CH:25]1[CH2:27][CH2:26]1)[CH2:21][CH2:22][CH3:23])[CH3:9].CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[NH:71]1[CH2:76][CH2:75][CH:74]([C:77]([O:79][CH2:80][CH3:81])=[O:78])[CH2:73][CH2:72]1>C1(C)C=CC=CC=1.[Cl-].[Na+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1)[CH2:6][N:7]([CH:8]([C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1[N:20]([CH2:24][CH:25]1[CH2:27][CH2:26]1)[CH2:21][CH2:22][CH3:23])[CH3:9])[C:28]1[N:33]=[CH:32][C:31]([N:71]2[CH2:76][CH2:75][CH:74]([C:77]([O:79][CH2:80][CH3:81])=[O:78])[CH2:73][CH2:72]2)=[CH:30][N:29]=1

Participants

8

Reactant 4

HCID 70770Ethyl 4-piperidinecarboxylateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86626853HCID 86626853, compound

Product 1

HCID 86626852HCID 86626852, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-{1-[2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethyl}-amine (200 mg) is dissolved in toluene (3 ml), and thereto are added tris(dibenzylideneacetone)dipalladium (27 mg), sodium tert-butoxide (42 mg), 2-(di-tert-butylphosphino)biphenyl (35 mg) and ethyl piperidine-4-carboxylate (66 μl) and the mixture is stirred at room temperature under nitrogen flow overnight. To the reaction solution are added a saturated brine, and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (hexane:ethyl acetate=19:1→21:4) to give ethyl 1-[2-((3,5-bis-trifluoromethyl-benzyl)-{1-[2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethyl}-amino)-pyrimidin-5-yl]-piperidine-4-carboxylate (78 mg). MS (m/z): 760 [M+H]+

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic layer is washed with a saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by column chromatography (hexane:ethyl acetate=19:1→21:4)

Sources & evidence

ORD record
ord-15bd8ecb6f2c4feba2ef6c89f48d86e6
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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