Nitrogen → tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate

HRID 454889Notes

Reaction equation

HRID 454889 reaction equation
[CH3:1][C:2]1([CH3:17])[C:6]([CH3:8])([CH3:7])[O:5][B:4](B2OC(C)(C)C(C)O2)[O:3]1.C([O-])(=O)C.[K+].N#N.FC(F)(F)S(O[C:31]1[CH2:32][CH2:33][CH2:34][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH:36]=1)(=O)=O.FC(F)(F)S(O[C:52]1[CH2:53][N:54]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH2:55][CH2:56][CH:57]=1)(=O)=O>O1CCOCC1.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].CCOC(C)=O.CCCCCC>[CH3:17][C:2]1([CH3:1])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:33]2[CH2:34][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:36][CH2:31][CH:32]=2)[O:3]1.[CH3:17][C:2]1([CH3:1])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:52]2[CH2:57][CH2:56][CH2:55][N:54]([C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])[CH:53]=2)[O:3]1

Participants

10

Reactant 5

HCID 947NitrogenHCID 517044Potassium AcetateHCID 10980453tert-Butyl 5-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydropyridine-1(2H)-carboxylateHCID 210362204,4,4',4',5,5,5'-Heptamethyl-2,2'-bi(1,3,2-dioxaborolane)HCID 53978067tert-Butyl 3-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate

Product 2

HCID 49835909Tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59327225tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylateYield 62.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
80 °C

Procedure

A flask with 4,4,4′,4′,5,5,5′-heptamethyl-2,2′-bi(1,3,2-dioxaborolane) (10.48 g, 43.7 mmol), (dppf)PdCl2 (0.930 g, 1.139 mmol), and potassium acetate (11.18 g, 114 mmol) was flushed with N2 (3×), then 1,4-dioxane (100 mL) was added followed by a solution of tert-butyl 5-(trifluoromethylsulfonyloxy)-3,4-dihydropyridine-1(2H)-carboxylate and tert-butyl 3-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (1:1 ratio, 12.58 g, 38.0 mmol) in 1,4-dioxane (100 mL). The solution was heated in an 80° C. oil bath for 20 hours. The reaction was quenched with water (100 mL) and the aqueous layer extracted with EtOAc (3×100 mL). The combined organic layers were washed with saturated aqueous NaCl (100 mL), dried with magnesium sulfate (MgSO4), and concentrated. The residue was purified by silica gel chromatography using ISCO™ (330 g SiO2, O-20% EtOAc/hexane) to give tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate and tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate (7.29 g, 23.58 mmol, 62.1% yield) (inseparable 2:1 mixture of olefin regioisomers) as a white solid.

Workup

  1. customThe reaction was quenched with water (100 mL)
  2. extractionthe aqueous layer extracted with EtOAc (3×100 mL)
  3. washThe combined organic layers were washed with saturated aqueous NaCl (100 mL)
  4. dry with materialdried with magnesium sulfate (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-0a68684428ed4627a31582c91a14fd9f
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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