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Cesium carbonate → Ethyl 4-[[6-(4-Hydroxy-4-Methyl-1-Piperidyl)-3-Methyl-Pyridine-2-carbonyl]amino]-3,5-dimethyl-benzoate

HRID 1427121
Notes
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Reaction equation

HRID 1427121 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[C:21]([CH3:22])=[CH:20][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:13][C:12]=2[CH3:23])=[O:9])[C:5]([CH3:24])=[CH:4][CH:3]=1.[CH3:25][C:26]1([OH:32])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:32][C:26]1([CH3:25])[CH2:31][CH2:30][N:29]([C:2]2[N:7]=[C:6]([C:8]([NH:10][C:11]3[C:21]([CH3:22])=[CH:20][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:13][C:12]=3[CH3:23])=[O:9])[C:5]([CH3:24])=[CH:4][CH:3]=2)[CH2:28][CH2:27]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 156491744-Methylpiperidin-4-olHCID 86707305Ethyl 4-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,5-dimethyl-benzoate

Product 1

HCID 86707351Ethyl 4-[[6-(4-Hydroxy-4-Methyl-1-Piperidyl)-3-Methyl-Pyridine-2-carbonyl]amino]-3,5-dimethyl-benzoate
Yield 80%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of ethyl 4-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,5-dimethyl-benzoate (275 mg, 792.93 μmoles), 4-methylpiperidin-4-ol (120 mg, 1.04 mmol) and Cs2CO3 (0.8 g, 2.46 mmol) in 1,4-dioxane (6 ml) is added Pd(OAc)2 (27 mg, 120.26 μmoles) followed by racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (54 mg, 86.72 μmoles). The reaction mixture is purged with nitrogen for 5 minutes and then heated to reflux. After 2 hours, the reaction is cooled to ambient temperature and diluted with ammonium chloride and extracted twice with EtOAc. The combined organic layers are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) using 0-70% ethyl acetate in hexane to afford the title compound as a yellow oil (0.27 g, 80%). Mass spectrum (m/z): 426.2 (M+1).

Workup

  1. customThe reaction mixture is purged with nitrogen for 5 minutes
  2. temperatureheated to reflux
  3. additiondiluted with ammonium chloride
  4. extractionextracted twice with EtOAc
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by flash chromatography (silica gel)

Sources & evidence

ORD record
ord-11795f4ace4e4095a5cbfe5a39bcbb31
Source dataset
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08933098B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes