1,2-Dimethoxyethane → 4-[2-(3,3,5,5-Tetramethylcyclohexyl)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester

HRID 32253

Reaction equation

HRID 32253 reaction equation
[CH3:1][C:2]1([CH3:24])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][CH:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2OS(C(F)(F)F)(=O)=O)[CH2:3]1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[C:25]([O:29][C:30]([N:32]1[CH2:33][CH:34]=[C:35]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH:4]2[CH2:3][C:2]([CH3:1])([CH3:24])[CH2:7][C:6]([CH3:8])([CH3:9])[CH2:5]2)[CH2:36][CH2:37]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59769399Trifluoromethanesulfonic acid 2-(3,3,5,5-tetramethylcyclohexyl)phenyl ester

Product 1

HCID 597694334-[2-(3,3,5,5-Tetramethylcyclohexyl)phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl esterYield 70.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of trifluoromethanesulfonic acid 2-(3,3,5,5-tetramethylcyclohexyl)phenyl ester (830 mg, 2.55 mmol) produced in Example (102c), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester (631 mg, 2.04 mmol) (Paul R. Eastwood, Tetrahedron Lett., 2000, 41, 3705) and 1,2-dimethoxyethane (20 mL) were added tetrakis(triphenylphosphine)palladium (147 mg, 0.13 mmol) and 2N aqueous solution of sodium carbonate (3.8 mL, 7.6 mmol), followed by stirring for 8 hours at an external temperature of 90° C. under a nitrogen atmosphere. Brine was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and the filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (ethyl acetate/heptane) to give 570 mg of the title compound as a light yellow oil.

Workup

  1. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe resultant residue was purified by silica gel column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-f748caf3779e4f65b93cca461b549b80
Source dataset
uspto-grants-2008_09
Patent number
US07425554B2

Linked notes

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