Triethylamine → HCID 71226405, compound

HRID 2409905Notes

Reaction equation

HRID 2409905 reaction equation
[CH3:1][C:2]1([C:17]([OH:19])=O)[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)[CH2:3]1.CC[N:22](CC)CC.C(Cl)(=O)OCC(C)C.[OH-].[NH4+]>C1COCC1>[CH3:1][C:2]1([C:17]([NH2:22])=[O:19])[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 62365Isobutyl chloroformateHCID 63136031HCID 63136031, compound

Product 1

HCID 71226405HCID 71226405, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-methyl-1-(4-nitrophenyl)piperidine-3-carboxylic acid (2.65 g, 10.03 mmol) in THF (45 ml) cooled at −5° C. (ice/NaCl bath) was added Et3N (1.537 mL, 11.03 mmol), followed by dropwise addition of isobutyl carbonochloridate (1.443mL, 11.03 mmol). After addition, the resulting yellow suspension was stirred at −3° C. for 75 min before 6.25 mL of 28% ammonium hydroxide aqueous solution (50 mmol, 5.0 equiv.) was added. The reaction mixture was stirred at ˜0° C. for 1.5 hrs. The reaction was quenched with water, the resulting mixture (pH>10) was extracted with EtOAc (3×). The combined organic phase was washed with water (2×), saturated aqueous NaCl (2×), dried over Na2SO4, filtered and concentrated. The crude product was crystallized from EtOAc to give title compound, 3-methyl-1-(4-nitrophenyl)piperidine-3-carboxamide (777 mg, 2.95 mmol, 29.4% yield) as a brown solid. Anal. Calcd. for C13H12N3O3 m/z 263.2, found: 264.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.20-8.02 (m, 2 H), 7.06-6.85 (m, 2 H), 3.91 (d, J=13.19 Hz, 1 H), 3.64-3.49 (m, 1 H), 3.16 (ddd, J=12.64, 8.25, 4.40 Hz, 1 H), 3.09 (s, 2 H), 3.06 (d, J=13.19 Hz, 1 H), 2.09 (d, J=13.74 Hz, 1 H), 1.91-1.72 (m, 2 H), 1.62-1.48 (m, 1 H), 1.25 (s, 3 H).

Workup

  1. additionAfter addition
  2. additionwas added
  3. customThe reaction was quenched with water
  4. extractionthe resulting mixture (pH>10) was extracted with EtOAc (3×)
  5. washThe combined organic phase was washed with water (2×), saturated aqueous NaCl (2×)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was crystallized from EtOAc

Sources & evidence

ORD record
ord-0caf7ad77e634725ab328b10ba2cdcfc
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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