Dichloromethane → 4-(4-pyrimidin-2-yl-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 1038051Notes

Reaction equation

HRID 1038051 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[K+].[K+].Br[C:36]1[N:41]=[CH:40][CH:39]=[CH:38][N:37]=1>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].O.C(OCC)(=O)C.CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:36]3[N:41]=[CH:40][CH:39]=[CH:38][N:37]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 783452-BromopyrimidineHCID 517044Potassium AcetateHCID 54371851Tert-butyl 4-(4-bromophenyl)-3,6-dihydropyridine-1(2h)-carboxylate

Product 1

HCID 669397234-(4-pyrimidin-2-yl-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

4-(4-Bromophenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (19.5 g, 0.058 mol), bis(pinacolate)diboron (22.0 g, 0.086 mol), PdCl2(dppf).CH2Cl2 (4.74 g, 0.0058 mol), potassium acetate (17.0 g, 0.17 mol) were weighted into a 1 L 2-necked round bottomed flask equipped with a reflux condenser. Methyl sulfoxide (400 ml) was added and the mixture was purged with nitrogen for 20 min before it was heated at 100° C. for 2 hr under nitrogen. The mixture was cooled to r.t. Potassium carbonate (40 g, 0.29 mol), 2-bromopyrimidine (11.0 g, 0.070 mol) and water (200 ml) were added. The mixture was again purged with nitrogen for 20 min. Palladium tetrakistriphenylphosphine (2.4 g, 0.0029 mol) was added and the final mixture was stirred at 100° C. for a further 2 hr. After being cooled to r.t., ethyl acetate and water were added. The mixture was filtered through a pad of Celite. Layers were separated and the organic layer was washed with water (×2). The combined aqueous layers were extracted with ethyl acetate (×1). The combined organic layers were stirred with enough charcoal to give a yellow solution. The mixture was filtered through a pad of Celite and the solvents in the filtrate were removed in vacuum to give 4-(4-pyrimidin-2-yl-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as dark brown oil.

Workup

  1. customequipped with a reflux condenser
  2. customthe mixture was purged with nitrogen for 20 min before it
  3. temperatureThe mixture was cooled to r.t
  4. customThe mixture was again purged with nitrogen for 20 min
  5. temperatureAfter being cooled to r.t.
  6. filtrationThe mixture was filtered through a pad of Celite
  7. customLayers were separated
  8. washthe organic layer was washed with water (×2)
  9. extractionThe combined aqueous layers were extracted with ethyl acetate (×1)
  10. customto give a yellow solution
  11. filtrationThe mixture was filtered through a pad of Celite
  12. customthe solvents in the filtrate were removed in vacuum

Sources & evidence

ORD record
ord-8614ddc4ed564b1698a6d4c069bea50d
Source dataset
uspto-grants-2013_10
Patent number
US08546404B2

Reaction notes

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