Dichloromethane → HCID 89748357, compound

HRID 1050528Notes

Reaction equation

HRID 1050528 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=2)O1.Br[C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1.C(Cl)Cl.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:28][C:27]1[CH:29]=[CH:30][C:24]([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:11][CH:10]=2)=[CH:25][C:26]=1[F:31]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 1230504-Bromo-2-fluoroanilineHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 89748357HCID 89748357, compoundYield 100.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (197, 1.95 g, 6.32 mmol), 4-bromo-2fluoroaniline (1.00 g, 5.26 mmol), Pd(dppf)Cl2.DCM (0.43 g, 0.526 mmol), K2CO3 (1.45 g, 10.5 mmol) were mixed in 40 mL dioxane and 20 mL water. The mixture was degassed with N2 stream for 3 min and stirred at 90° C. in N2 atmosphere for overnight. The mixture was cooled to RT, concentrated in vacuo, diluted with 120 mL EtOAc, washed with water ×2, dried, concentrated, and subjected to silica flash column to isolate tert-butyl 4-(4-amino-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate (198, 1.55 g, quantitative yield) using 0 to 25% EtOAc in hexane. It was dissolved in 150 mL iPrOH, and to it was hydrogenated with 10% Pd/C using a balloon for overnight. The mixture was filtered through celite, concentrated in vacuo to afford tert-butyl 4-(4-amino-3-fluorophenyl)piperidine-1-carboxylate (199) in quantitative yield.

Workup

  1. customThe mixture was degassed with N2 stream for 3 min
  2. temperatureThe mixture was cooled to RT
  3. concentrationconcentrated in vacuo
  4. additiondiluted with 120 mL EtOAc
  5. washwashed with water ×2
  6. customdried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4684d5ff1d7f4c7498f536a1eef32c23
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

Loading…