Sodium Carbonate → 4-(1-tert-Butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)benzoic acid

HRID 1264244Notes

Reaction equation

HRID 1264244 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:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)([OH:24])=[O:23].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>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(Cl)Cl.CCOCC>[C:22]([C:25]1[CH:30]=[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]=1)([OH:24])=[O:23]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 433294Lithium ChlorideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 227102704-(1-tert-Butoxycarbonyl-1,2,3,6-tetrahydropyridin-4-yl)benzoic acidYield 11.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 1,2,3,6-tetrahydro-4-[(trifluoromethyl)sulfonyloxy]pyridine-1-carboxylate (2.63 g, 7.9 mmol, reference example 76) in dimethdxyethane (21 mL) is added 4-carboxybenzeneboronic acid (1.44 g, 8.7 mmol), 2M aqueous sodium carbonate (17.4 mL) and lithium chloride (0.99 g, 24 mmol). The mixture is degassed and then tetrakis(triphenylphosphine)palladium (450 mg, 0.4 mmol) added, the reaction is degassed again and then heated at reflux 6 h. The reaction is filtered and the solid washed with EtOAc. The organic phase is washed with 0.5 N HCl, dried (MgSO4), concentrated and purified by column chromatography (silica, 3% MeOH/CH2Cl2/0.1%HOAc) providing a semi-purified product. This material is titurated with ether and a small amount of CH2Cl2 to provide 0.27 g of the title compound as a white solid: m.p. 200-209 (dec); 1H NMR (300 MHz, CDCl3) d 8.07 (d, J=8.4 Hz, 2H), 7.47 (d, J=8.4 Hz, 2H), 6.20 (bs, 1H), 4.15-4.00 (m, 2H), 3.66 (t, J=5.6 Hz, 2H), 2.60-2.52 (m, 2H), 1.50 (s, 9H); MS (ion spray) m/z 304 (M+H+).

Workup

  1. customThe mixture is degassed
  2. customthe reaction is degassed again
  3. temperatureheated
  4. temperatureat reflux 6 h
  5. filtrationThe reaction is filtered
  6. washthe solid washed with EtOAc
  7. washThe organic phase is washed with 0.5 N HCl
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. custompurified by column chromatography (silica, 3% MeOH/CH2Cl2/0.1%HOAc)
  11. customproviding a semi-purified product

Sources & evidence

ORD record
ord-2f5d1dacdf4e405a9596dc43f96d33ee
Source dataset
uspto-grants-2003_04
Patent number
US06541505B1

Reaction notes

Loading…