Piperidine → HCID 68996784, compound

HRID 2059699Notes

Reaction equation

HRID 2059699 reaction equation
[N:1]12[CH2:8][CH2:7][C:4]([CH:9]=[O:10])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.N1CCCCC1.[NH2:17][C:18]1[C:27](O)=[CH:26][CH:25]=[CH:24][C:19]=1[C:20]([O:22][CH3:23])=[O:21]>[Ag-]=O.CO>[N:1]12[CH2:8][CH2:7][C:4]([C:9]3[O:10][C:27]4[C:18](=[C:19]([C:20]([O:22][CH3:23])=[O:21])[CH:24]=[CH:25][CH:26]=4)[N:17]=3)([CH2:5][CH2:6]1)[CH2:3][CH2:2]2

Participants

6

Reactant 3

HCID 8082PiperidineHCID 205248Anthranilic acid, 3-hydroxy-, methyl esterHCID 22056677HCID 22056677, compound

Product 1

HCID 68996784HCID 68996784, compoundYield 21.3%

Reagents, catalysts & solvents 2

HCID 178418778HCID 178418778, compoundCatalystHCID 887MethanolSolvent

Procedure

A mixture of quinuclidine-4-carbaldehyde (0.57 g, 4.10 mmol), piperidine (0.86 g, 1 mL, 10.10 mmol), methyl 2-amino-3-hydroxybenzoate (0.68 g, 4.10 mmol) and methanol (10 mL) was heated to reflux for 40 h. Analysis by LCMS indicated the presence of the requisite intermediate Schiff base. The solvent was removed under reduced pressure, the residue was dissolved in methylene chloride (20 ml) and silver (I) oxide (1.23 g, 5.34 mmol) was added. The reaction mixture was stirred at room temperature for 5 h. Analysis by LCMS indicated consumption of the Schiff base intermediate. The reaction mixture was filtered though diatomaceous earth (10 g) eluting with methylene chloride (50 mL) and concentrated. The crude product was purified by column chromatography (silica gel, 5 to 20% methanol in chloroform) to afford methyl 2-(quinuclidin-4-yl)benzoxazole-4-carboxylate (250 mg, 17%) as an brown solid: 1H NMR (300 MHz, CDCl3) δ 7.96 (dd, J=8.0, 1.0 Hz, 1H), 7.67 (dd, J=8.0, 1.0 Hz, 1H), 7.37 (d, d, J=8.0 Hz, 1H), 4.01 (s, 3H), 3.06-3.02 (m, 6H), 2.06-2.01 (m, 6H); MS (ESI+) m/z 287 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 40 h
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe residue was dissolved in methylene chloride (20 ml)
  5. customconsumption of the Schiff base intermediate
  6. filtrationThe reaction mixture was filtered though diatomaceous earth (10 g)
  7. washeluting with methylene chloride (50 mL)
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography (silica gel, 5 to 20% methanol in chloroform)

Sources & evidence

ORD record
ord-999e7d44faba43588e8d8b689b9bd937
Source dataset
uspto-grants-2012_10
Patent number
US08278301B2

Reaction notes

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