Lithium Chloride → tert-butyl 4-(quinolin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1985492Notes

Reaction equation

HRID 1985492 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3](B(O)O)[CH:2]=1.FC(F)(F)S(O[C:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH:21]=1)(=O)=O.C(=O)(O)[O-].[Na+].[Cl-].[Li+]>C1(C)C=CC=CC=1.C(O)C.C(OCC)(=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>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH:21]=2)[CH:2]=1

Participants

9

Reactant 4

HCID 433294Lithium ChlorideHCID 516892Sodium BicarbonateHCID 2734663Quinoline-3-boronic acidHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 59731952tert-butyl 4-(quinolin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 76%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Quinolineboronic acid (250 mg, 1.4 mmol) and tert-butyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (580 mg, 1.8 mmol) were combined and dissolved in a mixture of toluene (10 mL) and ethanol (1 mL). 2M aqueous sodium bicarbonate solution (1.5 mL, 3.0 mmol) was added to the mixture followed by lithium chloride (180 mg, 4.2 mmol). Nitrogen gas was bubbled through the mixture for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (75 mg, 0.07 mmol) was added to the mixture. Reaction was heated at reflux for 3.5 hours. Mixture was cooled to room temperature and diluted with ethyl acetate (50 mL). Mixture was washed successively with water (2×30 mL) and brine (20 mL). Organic layer was dried (magnesium sulfate), filtered and concentrated in vacuo. Silica gel chromatography afforded the desired product as lightly colored oil in 76% yield. MS m/e (M−C4H8+H)+=255.1.

Workup

  1. customNitrogen gas was bubbled through the mixture for 10 minutes
  2. customReaction
  3. temperaturewas heated
  4. temperatureat reflux for 3.5 hours
  5. washMixture was washed successively with water (2×30 mL) and brine (20 mL)
  6. dry with materialOrganic layer was dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f2580d7d54754a7c94641ccf95213d75
Source dataset
uspto-grants-2009_06
Patent number
US07544680B2

Reaction notes

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