1,3-Dimethyl-2-imidazolidinone → HCID 178472355, compound

HRID 1893357Notes

Reaction equation

HRID 1893357 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[S:13][C:14](Br)=[C:15]([CH3:17])[N:16]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[Cl-].C[Zn+].[CH3:22]N1CCN(C)C1=O>C(N1C=CN(C(C)C)C1=[Pd-2](Cl)C1C(Cl)=CC=CN=1)(C)C.O1CCCC1>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[S:13][C:14]([CH3:22])=[C:15]([CH3:17])[N:16]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 66611,3-Dimethyl-2-imidazolidinoneHCID 178472352HCID 178472352, compoundHCID 178477797HCID 178477797, compound

Product 1

HCID 178472355HCID 178472355, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 178456357HCID 178456357, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of cis/trans-4-(5-bromo-4-methyl-thiazol-2-yl)-cyclohexanecarboxylic acid ethyl ester (1:5) (371 mg, 1.12 mmol) and 2 M methyl zinc chloride solution in tetrahydrofuran (0.837 ml, 1.67 mmol) in a 5:1 mixture of tetrahydrofuran and 1,3-dimethyl-2-imidazolidinone (6 ml) was added (1,3-diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium(II) chloride (15.2 mg, 22.3 μmol) at room temperature. The reaction mixture was heated at 50° C. for 2 h. After cooling to room temperature the reaction mixture was partitioned between tert-butyl methyl ether (25 ml) and 0.1 M aqueous sodium hydroxide solution (25 ml). The layers were separated. The aqueous layer was extracted with two 25-ml portions of tert-butyl methyl ether. The combined organic layers were washed with two 25-ml portions of water, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification with n-heptane/ethyl acetate as eluent gave the title compound (170 mg, 57%) as colorless oil, with a purity of 80% according to GC. MS m/e: 268 ([M+H]+)

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. customwas partitioned between tert-butyl methyl ether (25 ml) and 0.1 M aqueous sodium hydroxide solution (25 ml)
  3. customThe layers were separated
  4. extractionThe aqueous layer was extracted with two 25-ml portions of tert-butyl methyl ether
  5. washThe combined organic layers were washed with two 25-ml portions of water
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification with n-heptane/ethyl acetate as eluent

Sources & evidence

ORD record
ord-b9201a6d3824464fbecc039e3970b986
Source dataset
uspto-grants-2013_08
Patent number
US08513238B2

Reaction notes

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