Ethanol → HCID 68185444, compound

HRID 2366977Notes

Reaction equation

HRID 2366977 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+].CC1(C)C(C)(C)OB([C:37]2[CH:44]=[CH:43][C:40]([C:41]#[N:42])=[CH:39][CH:38]=2)O1.C(O)C>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.C1(C)C=CC=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:37]3[CH:44]=[CH:43][C:40]([C:41]#[N:42])=[CH:39][CH:38]=3)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3]

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 27346254-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 68185444HCID 68185444, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A flask was charged with 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, 0.542 mmol), potassium carbonate (150 mg, 1.083 mmol), tetrakis(triphenylphosphine)palladium(0) (6.26 mg, 5.42 μmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (149 mg, 0.650 mmol) then filled with ethanol (2 mL) and toluene (2 mL) and the resulting mixture was stirred under nitrogen at 90° C. for 16 h then cooled to room temperature and partitioned between water (20 mL) and EtOAc (60 mL). The layers were separated and the aqueous phase was extracted with EtOAc (30 mL). The combined organic phases were washed with brine (30 mL), dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 10 to 55% AcOEt in hexanes) gave 1-methylethyl[(2S,4R)-1-acetyl-6-(4-cyanophenyl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (176 mg, 0.45 mmol, 83%) as a white solid. LCMS (method G): Retention time 1.03 min, [M+H]+=392.0

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between water (20 mL) and EtOAc (60 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (30 mL)
  5. washThe combined organic phases were washed with brine (30 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash chromatography on silica gel (gradient: 10 to 55% AcOEt in hexanes)

Sources & evidence

ORD record
ord-7bf85ecd1f524167b1e537b3cf3500b1
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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