Triethylamine → Benzoylpiperidine

HRID 877884Notes

Reaction equation

HRID 877884 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-ba2357fced8f4f938549f3c11bc40eeb
Source dataset
uspto-grants-2015_03
Patent number
US08987303B2

Reaction notes

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