Benzophenone imine → HCID 86692535, compound

HRID 1748584Notes

Reaction equation

HRID 1748584 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:16]2[CH:21]=[CH:20][C:19](Br)=[CH:18][N:17]=2)([C:14]#[N:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C(O[Na])(C)(C)C.C(=[NH:71])(C1C=CC=CC=1)C1C=CC=CC=1.O.NO.C([O-])(=O)C.[Na+].C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:16]2[CH:21]=[CH:20][C:19]([NH2:71])=[CH:18][N:17]=2)([C:14]#[N:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

12

Reactant 7

HCID 136809Benzophenone imineHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 22235265HCID 22235265, compoundHCID 86692534HCID 86692534, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 86692535HCID 86692535, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of 4-(5-bromopyridin-2-yl)-4-cyanopiperidine-1-carboxylic acid tert-butyl ester (7.1 g), palladium(II) acetate (554 mg), (±)-2-(di-tert-butylphosphino)-1,1′-binaphthyl (1.51 g), and tert-butoxysodium (2.79 g) in toluene (48 ml) was added benzophenone imine (3.42 ml), stirred at 120° C. for 7 hours, then ethanol (48 ml), hydroxylamine monohydrate (5.4 g), and sodium acetate (9.54 g) were added thereto at room temperature, and stirred for 3.5 hours. To the reaction solution was added water (48 ml), stirred, then an aqueous solution of sodium hydrogen carbonate was added thereto, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and then the solvent was evaporated in vacuo. The obtained residue was purified with basic silica gel chromatography (n-hexane/ethyl acetate) to give 4-(5-aminopyridin-2-yl)-4-cyanopiperidine-1-carboxylic acid tert-butyl ester (4.0 g) as a white solid. 1H-NMR (DMSO-d6) δ (ppm): 1.40 (9H, s), 1.82-1.89 (2H, m), 2.08 (2H, J=12.8 Hz), 3.00 (2H, brs), 4.04 (2H, J=12.8 Hz), 6.96 (1H, dd, J=8.7, 3.1 Hz), 7.21 (1H, d, J=8.2 Hz), 7.92 (1H, d, J=2.6 Hz).

Workup

  1. stirringat room temperature, and stirred for 3.5 hours
  2. stirringstirred
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated in vacuo
  6. customThe obtained residue was purified with basic silica gel chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-29c1b1580cfa4490823ca67ee9cd96df
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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