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

HRID 643561Notes

Reaction equation

HRID 643561 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.[C:22]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)#[N: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>[C:22]([C:24]1[CH:29]=[C:28]([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:27]=[CH:26][CH:25]=1)#[N:23]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343253-Cyanophenylboronic acidHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 51356836tert-butyl 4-(3-cyanophenyl)-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; 3.24 g, 9.77 mmol), 3-cyanophenylboronic acid (2.01 g, 13.7 mmol), lithium chloride (1.23 g, 29.3 mmol), and 2 M Na2CO3 solution (14 mL) in DME (35 mL) was added Pd(PPh3)4 (564 mg, 0.489 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 ˜6 mL of 28% NH4OH solution. The layers were separated and the aqueous layer was extracted again with DCM. The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated. Purification by MPLC (silica, 45% ethyl acetate/hexanes eluent) afforded tert-butyl 4-(3-cyanophenyl)-3,6-dihydropyridine-1(2H)-carboxylate. 1HNMR (CDCl3, 500 MHz): δ 7.66 (s, 1H), 7.61 (dd, J=8.0, 1.5 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.46 (t, J=7.5 Hz, 1H), 6.13 (br s, 1H), 4.12 (m, 2H), 3.68 (t, J=5.5 Hz, 2H), 2.53 (br s, 2H), 1.52 (s, 9H).

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 ˜6 mL of 28% NH4OH solution
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted again with DCM
  10. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by MPLC (silica, 45% ethyl acetate/hexanes eluent)

Sources & evidence

ORD record
ord-149bd23e8d724eefa83b3832d2c44e9e
Source dataset
uspto-grants-2010_04
Patent number
US07700591B2

Reaction notes

Loading…