Ethyl 4-piperidinecarboxylate → 1-{2-[(3,5-Bis-trifluoromethyl-benzyl)-(2-fluoro-5-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yl}-ethyl piperidine-4-carboxylate

HRID 604020Notes

Reaction equation

HRID 604020 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([C:20]1[N:25]=[CH:24][C:23](Br)=[CH:22][N:21]=1)[CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[F:19].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].[NH:63]1[CH2:68][CH2:67][CH:66]([C:69]([O:71][CH2:72][CH3:73])=[O:70])[CH2:65][CH2:64]1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[NH:63]1[CH2:68][CH2:67][CH:66]([C:69]([O:71][CH:72]([C:23]2[CH:22]=[N:21][C:20]([N:7]([CH2:6][C:5]3[CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=[C:3]([C:2]([F:35])([F:34])[F:1])[CH:4]=3)[CH2:8][C:9]3[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[CH:11][C:10]=3[F:19])=[N:25][CH:24]=2)[CH3:73])=[O:70])[CH2:65][CH2:64]1

Participants

9

Reactant 5

HCID 70770Ethyl 4-piperidinecarboxylateHCID 516892Sodium BicarbonateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 86626777(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(2-fluoro-5-trifluoromethyl-benzyl)-amine

Product 1

HCID 866267791-{2-[(3,5-Bis-trifluoromethyl-benzyl)-(2-fluoro-5-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yl}-ethyl piperidine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(2-fluoro-5-trifluoromethyl-benzyl)-amine (300 mg) is dissolved in toluene (5 ml) and thereto are added tris(dibenzylideneacetone)dipalladium (48 mg), 2-(di-tert-butylphosphino)biphenyl (62 mg), sodium tert-butoxide (75 mg) and ethyl piperidine-4-carboxylate (120 μl) and the mixture is stirred under nitrogen atmosphere at room temperature overnight. To the reaction solution are added a saturated aqueous sodium bicarbonate solution and ethyl acetate, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=19:1→9:1) to give 1-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-fluoro-5-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yl}-ethyl piperidine-4-carboxylate (111 mg). MS (m/z): 653 [M+H]+

Workup

  1. customthe mixture is separated
  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 NH-silica gel column chromatography (hexane:ethyl acetate=19:1→9:1)

Sources & evidence

ORD record
ord-e7becac519f34a61a436106ad81391db
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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