Water → (4-Fluoro-phenyl)-(4-methyl-piperidin-4-yl)-methanone

HRID 1961639Notes

Reaction equation

HRID 1961639 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]([CH3:17])([C:14]([OH:16])=O)[CH2:10][CH2:9]1)(OC(C)(C)C)=O.[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(OC(=O)C(C)(C)C)(=O)C(C)(C)C.O>O1CCCC1.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:14]([C:11]2([CH3:17])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[O:16])=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 962WaterHCID 15234Pivalic anhydrideHCID 2856454-Fluorophenylboronic acidHCID 232828481-[(Tert-butoxy)carbonyl]-4-methylpiperidine-4-carboxylic acid

Product 1

HCID 20530715(4-Fluoro-phenyl)-(4-methyl-piperidin-4-yl)-methanoneYield 5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

N-boc-4-methyl-4-piperidinecarboxylic acid (4 g, 16 mol), 4-Fluorobenzeneboronic acid (2.7 g, 20 mol), Pivalic anhydride (4.6 g, 25 mmol), Pd(OAc)2(0.111 g, 0.4 mol), 1,1′-Bis(diphenylphosphino)ferrocene (0.319 g, 0.1 mol) and (0.7 mL, 41 mmol) of water are mixed together in 20 mL of tetrahydrofuran and the mixture heated at 60° C. overnight. The reaction mixture was filtrated and the solvent was removed under vacuum. The residue was purified with column chromatography on silica using n-heptane-EtOAc (4:1) to yield 0.216 g (5%) of the title compound. MS (m/e): 322.0 (M+H+).

Workup

  1. filtrationThe reaction mixture was filtrated
  2. customthe solvent was removed under vacuum
  3. customThe residue was purified with column chromatography on silica

Sources & evidence

ORD record
ord-e42ad3e2b3d845f69c8efd799c89909e
Source dataset
uspto-grants-2013_04
Patent number
US08415350B2

Reaction notes

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