Hydrochloric Acid → 4-(5-Aminopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile

HRID 1748519Notes

Reaction equation

HRID 1748519 reaction equation
C(=[NH:14])(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:16]1[CH:17]=[CH:18][C:19]([C:22]2([C:33]#[N:34])[CH2:27][CH2:26][N:25]([CH2:28][C:29]([OH:32])([CH3:31])[CH3:30])[CH2:24][CH2:23]2)=[N:20][CH:21]=1.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].Cl.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[NH2:14][C:16]1[CH:17]=[CH:18][C:19]([C:22]2([C:33]#[N:34])[CH2:27][CH2:26][N:25]([CH2:28][C:29]([OH:32])([CH3:31])[CH3:30])[CH2:24][CH2:23]2)=[N:20][CH:21]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 136809Benzophenone imineHCID 516892Sodium BicarbonateHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 23676156Sodium t-butoxideHCID 866924674-(5-Bromopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile

Product 1

HCID 866924684-(5-Aminopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrileYield 81.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

Benzophenonimine (2.22 g) was added to a suspension of 4-(5-bromopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile (3.95 g), palladium (II) acetate (328 mg), racemic-2-(di-tert-butylphosphino)-1,1′-binaphthyl (909 mg) and sodium tert-butoxide (1.68 g) in toluene (29 ml), and stirred at 120° C. for 2.5 hours. The reaction solution was left stand, a mixture of concentrated hydrochloric acid (2 ml) and water (6 ml) were added at 60-80° C. and stirred at room temperature. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified with basic silica gel column chromatography (n-hexane/ethyl acetate) to give the titled compound (2.6 g) as a pale yellow solid.

Workup

  1. waitThe reaction solution was left stand
  2. additionwere added at 60-80° C.
  3. stirringstirred at room temperature
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified with basic silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-407f97cfb8a643a19128679650219744
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

Loading…