Piperidine → Benzoic Acid

HRID 468694Notes

Reaction equation

HRID 468694 reaction equation
N1CCCCC1.FC(F)OC1C(OC)=CC(C=O)=CC=1OC.C(CC(N[C:30]1[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=1[C:32]([OH:34])=[O:33])=O)(O)=O>C1(C)C=CC=CC=1>[C:32]([OH:34])(=[O:33])[C:31]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:30]=1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 4399222-(2-Carboxyacetamido)benzoic acidHCID 7105984-(Difluoromethoxy)-3,5-dimethoxybenzaldehyde

Product 1

HCID 243Benzoic AcidYield 163.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Piperidine (110 μL, 1.10 mmol) was added to a suspension of 4-(difluoromethoxy)-3,5-dimethoxybenzaldehyde (200 mg, 1.10 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (233 mg, 1.05 mmol) in toluene (5.0 mL). The reaction flask was fitted with a Dean-Stark apparatus and heated to reflux for 30 min. The reaction was then cooled to rt and the resulting suspension was filtered and washed with toluene. The piperidinium salt was dissolved in MeOH (4 mL) and water (2 mL) and the solution was acidified with 20% aqueous AcOH. The crude product was collected by filtration and recrystallised from EtOH/water and filtered to afford (E)-2-[[4-(difluoromethoxy)-3,5-dimethoxyphenyl)-1-oxo-2-propenyl]amino]benzoic acid (210 mg, 51%) as a pale yellow crystalline solid; mp 211-215° C.; δH (400 MHz, DMSO-d6) 3.87 (s, 6H, OCH3), 6.87 (t, J=75 Hz, 1H, OCHF2), 6.98 (d, J=15.6 Hz, 1H, CH═CHCO), 7.17 (s, 2H, H2′, H6′), 7.18 (t, J4,5=J5,6=8.0 Hz, 1H, H5), 7.61 (d, J=15.6 Hz, 1H, CH═CHCO), 7.62 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 8.00 (d, J5,6=8.0 Hz, 1H, H6), 8.61 (d, J3,4=8.0 Hz, 1H, H3), 11.33 (s, 1H, NH), 13.60 (s, 1H, CO2H); δC (100 MHz, DMSO-d6) 56.4, 105.5, 116.8 117.2 (t, J=259 Hz), 120.4, 122.9, 123.1, 129.6, 131.1, 132.9, 134.0, 140.8, 141.1, 152.6, 163.7, 169.4; νmax 1153, 1113, 1224, 1506, 1593, 1694, 2602, 2946 cm−1.

Workup

  1. customThe reaction flask was fitted with a Dean-Stark apparatus
  2. temperatureheated
  3. temperatureto reflux for 30 min
  4. filtrationthe resulting suspension was filtered
  5. washwashed with toluene
  6. dissolutionThe piperidinium salt was dissolved in MeOH (4 mL)
  7. filtrationThe crude product was collected by filtration
  8. customrecrystallised from EtOH/water
  9. filtrationfiltered

Sources & evidence

ORD record
ord-8046a0cd47c04c2cada7212502fd3dff
Source dataset
uspto-grants-2014_01
Patent number
US08624056B2

Reaction notes

Loading…