Potassium Carbonate → HCID 86669254, compound

HRID 2366915Notes

Reaction equation

HRID 2366915 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3].C(=O)([O-])[O-].[K+].[K+].[CH3:29][C:30]1[S:31][C:32](B2OC(C)(C)C(C)(C)O2)=[C:33]([CH3:35])[N:34]=1>C(O)C.C1(C)C=CC=CC=1.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>[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:32]3[S:31][C:30]([CH3:29])=[N:34][C:33]=3[CH3:35])[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 185257002,4-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazoleHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 86669254HCID 86669254, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

1-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (for a preparation see Example 61) (100 mg, 0.271 mmol) were dissolved in ethanol (1 mL) and Toluene (1 mL), mixed with potassium carbonate (74.9 mg, 0.542 mmol), 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboroian-2-yl)-1,3-thiazole (78 mg, 0.325 mmol, available from Maybridge), followed by tetrakis(triphenylphosphine)palladium(0) (15.65 mg, 0.014 mmol) and refluxed under nitrogen at 90° C. for 18.5 hours reaction time. The reaction mixture was partitioned between distilled water (40 mL) and EtOAc (40 mL). The organic and aqueous layers were run off and the latter extracted twice more using EtOAc (2×40 mL). Organic fractions were combined, dried (brine (80 mL) and sodium sulfate), filtered and evaporated to dryness to give a pale white solid (0.123 g). This was purified on a 25+M Biotage silica column, eluting with cyclohexane:EtOAc (1:0 to 1:3). Product-containing fractions were evaporated to dryness to give a clear, colourless solid which was repurified on a 12+M column using the same solvent system. Analysis of the product still showed contamination and it was further purified using MDAP. Product-containing fractions were evaporated to dryness to give a clear, colourless solid (41 mg). LCMS (Method C): Rt=0.76, MH+=402

Workup

  1. customreaction time
  2. customThe reaction mixture was partitioned
  3. distillationbetween distilled water (40 mL) and EtOAc (40 mL)
  4. extractionthe latter extracted twice more
  5. dry with materialdried (brine (80 mL) and sodium sulfate)
  6. filtrationfiltered
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-61eb62b22cd34d2890fc14409c0f889f
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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