Sodium Carbonate → tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate

HRID 643533Notes

Reaction equation

HRID 643533 reaction equation
FC(F)(F)S(O[C:7]1[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH:12]=1)(=O)=O.[CH2:22]([O:24][C:25]([C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1)=[O:26])[CH3:23].[Cl-].[Li+].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:22]([O:24][C:25]([C:27]1[CH:32]=[C:31]([C:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH:12]=2)[CH:30]=[CH:29][CH:28]=1)=[O:26])[CH3:23]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 3249312(3-Ethoxycarbonylphenyl)boronic acidHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 57880536tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of tert-butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylate (prepared according to Wustrow, D. J., Wise, L. D., Synthesis, (1991), 993-995.; 10.5 g, 31.6 mmol), 3-(ethoxycarbonyl)phenylboronic acid (8.59 g, 44.3 mmol), lithium chloride (3.98 g, 94.8 mmol), and 2 M Na2CO3 solution (44 mL) in DME (107 mL) was added Pd(PPh3)4 (1.82 g, 1.58 mmol), and the resulting mixture was stirred at reflux under a nitrogen atmosphere for 3.5 h. The reaction mixture was cooled to rt, stirred overnight, then partially concentrated to remove most of the DME. To the remaining aqueous mixture was added DCM, 2M Na2CO3 solution, and ˜10 mL of 28% NH4OH solution. The layers were separated and the organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 10% ethyl acetate/hexanes eluent) afforded tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate. 1HNMR (CDCl3, 500 MHz): δ 8.07 (s, 1H), 7.95 (d, J=7.5 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.43 (t, J=8.0 Hz, 1H), 6.13 (br s, 1H), 4.41 (q, J=7.0 Hz, 2H), 4.12 (br s, 2H), 3.68 (t, J=5.5 Hz, 2H), 2.58 (br s, 2H), 1.52 (s, 9H), 1.43 (t, J=7.0 Hz, 3H).

Workup

  1. customprepared
  2. custom, Synthesis, (1991), 993-995
  3. temperatureat reflux under a nitrogen atmosphere for 3.5 h
  4. stirringstirred overnight
  5. concentrationpartially concentrated
  6. customto remove most of the DME
  7. additionTo the remaining aqueous mixture was added DCM, 2M Na2CO3 solution, and ˜10 mL of 28% NH4OH solution
  8. customThe layers were separated
  9. washthe organic layer was washed with brine
  10. dry with materialdried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by flash chromatography (silica, 10% ethyl acetate/hexanes eluent)

Sources & evidence

ORD record
ord-b49a65bc6065419f960501c9906bed75
Source dataset
uspto-grants-2010_04
Patent number
US07700591B2

Reaction notes

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