Potassium Carbonate → HCID 52934330, compound

HRID 2366943Notes

Reaction equation

HRID 2366943 reaction equation
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:43][C:44]1[N:45]=[CH:46][NH:47][CH:48]=1.[CH3:49][CH:50]([O:52][C:53](=[O:70])[NH:54][C@H:55]1[C:64]2[C:59](=[CH:60][CH:61]=[C:62](Br)[CH:63]=2)[N:58]([C:66](=[O:68])[CH3:67])[C@@H:57]([CH3:69])[CH2:56]1)[CH3:51].C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)(C)(C)C>[C:66]([N:58]1[C:59]2[C:64](=[CH:63][C:62]([N:47]3[CH:48]=[C:44]([CH3:43])[N:45]=[CH:46]3)=[CH:61][CH:60]=2)[C@H:55]([NH:54][C:53](=[O:70])[O:52][CH:50]([CH3:49])[CH3:51])[CH2:56][C@@H:57]1[CH3:69])(=[O:68])[CH3:67]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamateHCID 178418800HCID 178418800, compound

Product 1

HCID 52934330HCID 52934330, compoundYield 1.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

A stock solution of tert-butanol (5 mL) and water (10 μl) was prepared and degassed under house vacuum and quenched several times with nitrogen. A mixture of palladium(II) acetate (6 mg, 5 mmol) and Xantphos (38 mg, 0.081 mmol) in the stock solvent (4 mL) was heated at 80° C. for 1 min under microwave irradiation then cooled to room temperature. The solution was then added to a mixture of 4-methylimidazole (53 mg, 0.65 mmol), 1-methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Example 4) (200 mg, 0.54 mmol) and potassium carbonate (112 mg, 0.81 mmol). The resulting mixture was stirred at 110° C. for 15 h under microwave irradiation then cooled to room temperature and the insoluble were filtered off. Most of the solvents were removed in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM) gave 1-methylethyl [(2S,4R)-1-acetyl-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (3 mg, 0.0081 mmol, 1.5%)

Workup

  1. customdegassed under house vacuum
  2. customquenched several times with nitrogen
  3. temperaturethen cooled to room temperature
  4. customfor a preparation
  5. temperaturethen cooled to room temperature
  6. filtrationthe insoluble were filtered off
  7. customMost of the solvents were removed in vacuo
  8. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM)

Sources & evidence

ORD record
ord-e33dbc2f808945b18cf46564ffd59661
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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