Piperidine → 3-Bromobenzoic acid

HRID 468686Notes

Reaction equation

HRID 468686 reaction equation
N1CCCCC1.FC(F)OC1C=C(C=CC=1OC(F)F)C=O.C(CC(N[C:30]1[CH:38]=[CH:37][C:36]([Br:39])=[CH:35][C:31]=1[C:32]([OH:34])=[O:33])=O)(O)=O>C1(C)C=CC=CC=1>[Br:39][C:36]1[CH:37]=[CH:38][CH:30]=[C:31]([CH:35]=1)[C:32]([OH:34])=[O:33]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 145092693,4-Bis(difluoromethoxy)benzaldehydeHCID 593338562-[(Carboxyacetyl)amino]-5-bromobenzoic acid

Product 1

HCID 114563-Bromobenzoic acidYield 107.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Piperidine (100 μL, 1.01 mmol) was added to a suspension of 3,4-bis(difluoromethoxy)benzaldehyde (240 mg, 1.01 mmol) and 2-[(carboxyacetyl)amino]-5-bromobenzoic acid (277 mg, 0.92 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 (5 mL) and water (2 mL) and the solution was acidified with 50% aqueous AcOH. The crude product was collected by filtration and recrystallised from EtOH/water and filtered to afford (E)-2-[[3,4-bis(difluoromethoxy)phenyl)-1-oxo-2-propenyl]amino]-5-bromobenzoic acid (198 mg, 45%) as a colourless crystalline solid; mp 223-226° C.; δH (400 MHz, DMSO-d6) 6.96 (d, J=15.6 Hz, 1H, CH═CHCO), 7.26 (t, J=73 Hz, 1H, OCHF2), 7.27 (t, J=73 Hz, 1H, OCHF2), 7.38 (d, J5′,6′=8.0 Hz, 1H, H5′), 7.61 (d, J=15.6 Hz, 1H, CH═CHCO), 7.68 (dd, J5′,6′=8.0, J2′,6′=1.6 Hz, 1H, H6′), 7.78 (d, J2′,6′=1.6 Hz, 1H, H2′), 7.80 (dd, J3,4=9.2, J4,6=2.8 Hz, 1H, H4), 8.08 (d, J4,6=2.8 Hz, 1H, H6), 8.55 (d, J3,4=9.2 Hz, 1H, H3), 11.28 (s, 1H, NH); δC (100 MHz, DMSO-d6) 116.3 (t, J=259 Hz), 116.5 (t, J=259 Hz), 116.5, 119.3, 120.1, 120.8, 122.6, 123.5, 126.7, 132.7, 133.2, 136.4, 139.7, 139.8, 141.9, 142.8, 163.6, 168.0; HRMS (ESL) calculated for C18H12BrF4NO5 [M-H ]− 475.9751, found 475.9752; νmax 1102, 1152, 1509, 1595, 1673, 1694, 3128 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 (5 mL)
  7. filtrationThe crude product was collected by filtration
  8. customrecrystallised from EtOH/water
  9. filtrationfiltered

Sources & evidence

ORD record
ord-558924b471d247d085d7bb636d2b7dfa
Source dataset
uspto-grants-2014_01
Patent number
US08624056B2

Reaction notes

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