Potassium Carbonate → tert-butyl 4-(3-methoxy-4-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 705741Notes

Reaction equation

HRID 705741 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=1.CC1(C)C(C)(C)OB([C:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH:22]=2)O1.C(=O)([O-])[O-].[K+].[K+].[Cl-].[Li+]>CN(C=O)C>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([C:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH:22]=2)[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 433294Lithium ChlorideHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 117464905-Bromo-2-nitroanisole

Product 1

HCID 56945492tert-butyl 4-(3-methoxy-4-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 4-bromo-2-methoxy-1-nitrobenzene, (I24) (2.364 g, 10.2 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (3.00 g, 9.70 mmol), potassium carbonate (4.02 g, 29.1 mmol) and DMF (60 mL) was degassed with three vacuum/nitrogen cycles then PdCl2(dppf)-DCM solvate (450 mg, 6 mol %) added under nitrogen in a Schlenk tube. A second tube was prepared in the same manner (i.e. a total of 6.00 g starting boronate), and both tubes were heated to 85° C. under nitrogen. After 17 hours both tubes were cooled under nitrogen and added to 5% w/v aqueous lithium chloride (600 mL). The resulting mixture was extracted with ether (300 mL) and ethyl acetate (3×300 mL). The combined organic extracts were washed with water (600 mL) and brine (600 mL), dried (sodium sulphate) then evaporated to dryness. The residue was chromatographed (120 g silica cartridge, 0-60% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I25) (5.863 g, 91% yield) as a yellow solid; 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J=8.5 Hz, 1H), 7.04-6.97 (m, 2H), 6.17 (s, 1H), 4.12 (d, J=2.5 Hz, 2H), 3.98 (s, 3H), 3.65 (t, J=5.6 Hz, 2H), 2.52 (s, 2H), 1.49 (s, 9H). LCMS Method C: rt 6.27 min; m/z 279.0 [M-tBu+2H]+, 235.1 [M-Boc+2H]+.

Workup

  1. customwas degassed with three vacuum/nitrogen cycles
  2. additionPdCl2(dppf)-DCM solvate (450 mg, 6 mol %) added under nitrogen in a Schlenk tube
  3. customA second tube was prepared in the same manner (i.e. a total of 6.00 g starting boronate), and both tubes
  4. temperatureAfter 17 hours both tubes were cooled under nitrogen
  5. additionadded to 5%
  6. extractionThe resulting mixture was extracted with ether (300 mL) and ethyl acetate (3×300 mL)
  7. washThe combined organic extracts were washed with water (600 mL) and brine (600 mL)
  8. dry with materialdried (sodium sulphate)
  9. customthen evaporated to dryness
  10. customThe residue was chromatographed (120 g silica cartridge, 0-60% ethyl acetate/petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-dad1b5e93bc846eb9b9bf6c4000538d1
Source dataset
uspto-grants-2015_11
Patent number
US09174946B2

Reaction notes

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