1,2-Dimethoxyethane → 4-[5-Fluoro-2-(3,3,5,5-tetramethylcyclohex-1-enyl)phenyl]piperidine-1-carboxylic acid t-butyl ester

HRID 32266Notes

Reaction equation

HRID 32266 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2OS(C(F)(F)F)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:37]2[CH2:42][C:41]([CH3:44])([CH3:43])[CH2:40][C:39]([CH3:46])([CH3:45])[CH:38]=2)O1.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:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[C:37]2[CH2:42][C:41]([CH3:44])([CH3:43])[CH2:40][C:39]([CH3:46])([CH3:45])[CH:38]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 231420594,4,5,5-Tetramethyl-2-(3,3,5,5-tetramethylcyclohex-1-en-1-yl)-1,3,2-dioxaborolaneHCID 597694544-(5-Fluoro-2-trifluoromethanesulfonyloxyphenyl)piperidine-1-carboxylic acid t-butyl ester

Product 1

HCID 597693864-[5-Fluoro-2-(3,3,5,5-tetramethylcyclohex-1-enyl)phenyl]piperidine-1-carboxylic acid t-butyl esterYield 48.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

To a mixture of 4-(5-fluoro-2-trifluoromethanesulfonyloxyphenyl)piperidine-1-carboxylic acid t-butyl ester (523 mg, 1.22 mmol) produced in Example (106e), 4,4,5,5-tetramethyl-2-(3,3,5,5-tetramethylcyclohex-1-enyl)[1,3,2]dioxaborolane (387 mg, 1.46 mmol) produced in Example (4b) and 1,2-dimethoxyethane (10 mL) were added tetrakis(triphenylphosphine)palladium(0) (71 mg, 0.06 mmol) and 2N aqueous solution of sodium carbonate (1.83 ml, 3.66 mmol), followed by stirring for 1 hour and 30 minutes 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 to give a residue, which was purified by silica gel column chromatography (ethyl acetate/heptane) to give 245 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. customto give a residue, which
  4. customwas purified by silica gel column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-13655e7b3f9f42839fd70287a2eded10
Source dataset
uspto-grants-2008_09
Patent number
US07425554B2

Reaction notes

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