Sodium Carbonate → 4-[2-(4-Chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 410341Notes

Reaction equation

HRID 410341 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH2:20][C:19]([CH3:22])([CH3:21])[CH2:18][CH2:17][C:16]=2Br)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+]>CO.O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH2:20][C:19]([CH3:22])([CH3:21])[CH2:18][CH2:17][C:16]=2[C:28]2[CH:29]=[CH:30][C:25]([Cl:24])=[CH:26][CH:27]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 67422645Tert-butyl 4-((2-bromo-5,5-dimethylcyclohex-1-enyl)methyl)piperazine-1-carboxylate

Product 1

HCID 672260044-[2-(4-Chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazine-1-carboxylic acid tert-butyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 21966525Dioxane MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 4-(2-bromo-5,5-dimethyl-cyclohex-1-enylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (1.3 g, 3.36 mmol) and 4-chlorophenyl boronic acid (0.78 g, 5.04 mmol) in 2:1 MeOH/1,4-dioxane (20 ml) at rt was added a solution of 2M Na2CO3 (3.3 ml, 6.72 mmol). Nitrogen was bubbled through the mixture for 2 min and then PdCl2[dppf] (200 mg, 0.28 mmol) was added. The reaction flask was sealed and heated to 100° C. where it was maintained for 1 h. After this time the suspension was cooled to rt and filtered through Celite®. The collected solids were washed with additional dichloromethane and the combined filtrate and washings were concentrated under reduced pressure. Purification by column chromatography on silica eluting with 6% EtOAc/heptanes gave 4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazine-1-carboxylic acid tert-butyl ester (1.0 g, 71%). HPLC-MS 419, 421 [M+1]+.

Workup

  1. customNitrogen was bubbled through the mixture for 2 min
  2. customThe reaction flask was sealed
  3. temperaturewas maintained for 1 h
  4. temperatureAfter this time the suspension was cooled to rt
  5. filtrationfiltered through Celite®
  6. washThe collected solids were washed with additional dichloromethane
  7. concentrationthe combined filtrate and washings were concentrated under reduced pressure
  8. customPurification by column chromatography on silica eluting with 6% EtOAc/heptanes

Sources & evidence

ORD record
ord-8e88aae6d2584fd4a0b6f18f03086907
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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