Triethylamine → Benzoylpiperidine

HRID 2407624Notes

Reaction equation

HRID 2407624 reaction equation
Cl.CO[C:4]1[CH:17]=[CH:16][C:7]([C:8](C2CCNCC2)=[O:9])=[CH:6][CH:5]=1.COC([C:22]1[CH:23]=[CH:24][C:25](C(O)=O)=[N:26][CH:27]=1)=O.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[C:8]([N:26]1[CH2:27][CH2:22][CH2:23][CH2:24][CH2:25]1)(=[O:9])[C:7]1[CH:6]=[CH:5][CH:4]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 3149925-(Methoxycarbonyl)pyridine-2-carboxylic acidHCID 27405874-(4-Methoxybenzoyl)piperidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 69892BenzoylpiperidineYield 161.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-(4-methoxybenzoyl)piperidine hydrochloride (2.00 g, 7.82 mmol, 1.0 eq) and 5-(methoxycarbonyl)pyridine-2-carboxylic acid (1.42 g, 7.82 mmol, 1.0 eq) in dimethylformamide (55 mL) was added triethylamine (2.72 mL, 19.55 mmol, 2.5 eq) followed by HATU (2.97 g, 7.82 mmol, 1.0 eq). The reaction was stirred at room temperature for 4 hours before partitioning between EtOAc (250 mL) and water-NaHCO3 (1:1, 200 mL). The organics were further washed with brine (150 mL), water (150 mL) and brine (150 mL), dried (Na2SO4) and concentrated under reduced pressure. Column chromatography (silica, 4-5% MeOH—CH2Cl2) yielded the coupled product (2.39 g, 80%) as a white foam; 1H nmr (CDCl3) δ 9.08 (1H, m, pyH-6), 8.29 (1H, dd, J 8.5, 2.0 Hz, pyH-4), 7.84 (2H, d, J 9.0 Hz, 2H of C6H4OCH3), 7.60 (1H, d, J 8.0 Hz, pyH-3), 6.84 (2H, d, J 9.0 Hz, 2H of C6H4OCH3), 4.60 (1H, m, 1H of BzpipH-2, H-6), 3.87 (3H, s, 1×OCH3), 3.82 (1H, m, 1H of BzpipH-2, H-6), 3.77 (3H, s, 1×OCH3), 3.46 (1H, m, BzpipH-4), 3.19 (1H, ddd, J 14.0, 10.0, 4.0 Hz, 1H of BzpipH-2, H-6), 3.02 (1H, m, 1H of BzpipH-2, H-6), 1.95-1.90 (1H, m, 1H of BzpipH-3, H-5), 1.83-1.79 (3H, m, 3H of BzpipH-3, H-5); 13C nmr (CDCl3) δ 199.9, 166.6, 165.0, 163.5, 157.7, 149.6, 138.1, 130.5, 128.5, 126.3, 123.1, 113.9, 55.4, 52.5, 46.6, 42.6, 41.8, 28.8, 28.4; m/z: 383 [M+H]+ (found [M+H]+, 383.1515, C21H22N2O5 requires [M+H]+ 383.1602).

Workup

  1. custombefore partitioning between EtOAc (250 mL) and water-NaHCO3 (1:1, 200 mL)
  2. washThe organics were further washed with brine (150 mL), water (150 mL) and brine (150 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-41abf79ba3594976990424177ad489ae
Source dataset
uspto-grants-2014_08
Patent number
US08809370B2

Reaction notes

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