Potassium Carbonate → tert-butyl 4-(3-bromophenyl)-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1809795Notes

Reaction equation

HRID 1809795 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26](I)[CH:25]=1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:26]2[CH:27]=[CH:28][CH:29]=[C:24]([Br:23])[CH:25]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 11561Benzene, 1-bromo-3-iodo-HCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 66836951tert-butyl 4-(3-bromophenyl)-3,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A stirred mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (prepared as described in Tetrahedron Letters 2000, 3705-3708; 6.52 g, 21.1 mmol), 1-bromo-3-iodobenzene (4.05 mL, 31.8 mmol), bis-(triphenyl-phosphine)-palladium(II) chloride (892 mg, 1.27 mmol), K2CO3 (8.7 g, 63 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (704 mg, 1.27 mmol) in 120 mL dimethylformamide is heated at 80° C. under argon for 14 h. The mixture is cooled to RT, dimethylformamide is removed in vacuo. After addition of brine, the aqueous layer is extracted three times with CH2Cl2. The combined organic extracts are dried (Na2SO4) and evaporated in vacuo. Flash chromatography of the residue (SiO2, hexane/ethyl acetate) affords 4-(3-bromo-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester as a colourless viscous resin: MS 338.2/340.2 [M+H]+; retention time 8.01 min (HPLC, Nucleosil C18; 5→100% CH3CN in H2O within 8 min, then 100% CH3CN for 2 min).

Workup

  1. temperatureThe mixture is cooled to RT
  2. customdimethylformamide is removed in vacuo
  3. additionAfter addition of brine
  4. extractionthe aqueous layer is extracted three times with CH2Cl2
  5. dry with materialThe combined organic extracts are dried (Na2SO4)
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-9358ead3e5824935b75e00ab74418a2c
Source dataset
uspto-grants-2013_01
Patent number
US08362040B2

Reaction notes

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