Sodium Carbonate → tert-butyl 4-(4-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 380478Notes

Reaction equation

HRID 380478 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11](OS(C(F)(F)F)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+].[Li+].[Cl-]>C(COC)OC.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:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:27]2[CH:28]=[CH:29][C:24]([C:23]([F:34])([F:33])[F:22])=[CH:25][CH:26]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 18364827tert-butyl 4-(4-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 61.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 0.66 g (2 mmol) of 1-t-butoxycarbonyl-4-trifluoromethylsulfonyloxy-1,2,3,6-tetrahydropyridine and 0.57 g (6 mmol) of 4-trifluoromethylphenylboronic acid in 6 mL of DME (dimethoxyethane) was added 2.5 mL (5 mmol) of a 2M solution of Na2CO3, 0.24 g (6 mmol) of LiCl and 0.115 g (0.1 mmol) of Pd(PPh3)4 and the reaction mixture was heated at reflux for 4 h. The reaction mixture was concentrated and dissolved in 10 mL of CH2Cl2. The solution was washed with sat'd NaHCO3 solution, dried over Na2SO4, filtered and the filtrate was concentrated. The residue was purified by chomatography (silica, hexanes: ethyl acetate, 10:1) to give 0.4 g of the title compound. 1H NMR (CDCl3) δ1.51 (s, 9H), 2.54 (m, 2H), 3.67 (t, 2H, J=6 Hz), 4.12 (br, 2H), 6.14 (br, 1H), 7.47 (d, 2H, J=8 Hz), 7.59 (d, 2H, J=8 Hz);

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 4 h
  3. concentrationThe reaction mixture was concentrated
  4. dissolutiondissolved in 10 mL of CH2Cl2
  5. washThe solution was washed with sat'd NaHCO3 solution
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customThe residue was purified by chomatography (silica, hexanes: ethyl acetate, 10:1)

Sources & evidence

ORD record
ord-0425cb54cb654fa595ddad485de075cd
Source dataset
uspto-grants-2001_10
Patent number
US06303593B1

Reaction notes

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