N-(2-hydroxyethyl)nicotinamide → 4-Phenyl-Butyric Acid 2-[(Pyridine-3-Carbonyl)Amino]-Ethyl Ester

HRID 1092931Notes

Reaction equation

HRID 1092931 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[N:8][CH:7]=1.[C:13]1([CH2:19][CH2:20][CH2:21][C:22](Cl)=[O:23])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(Cl)Cl.N1C=CC=CC=1>[N:8]1[CH:9]=[CH:10][CH:11]=[C:6]([C:5]([NH:4][CH2:3][CH2:2][O:1][C:22](=[O:23])[CH2:21][CH2:20][CH2:19][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:12])[CH:7]=1

Participants

5

Reactant 2

HCID 72663N-(2-hydroxyethyl)nicotinamideHCID 117898654-Phenylbutanoyl Chloride

Product 1

HCID 161137614-Phenyl-Butyric Acid 2-[(Pyridine-3-Carbonyl)Amino]-Ethyl EsterYield 100%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2 °C

Procedure

N-(2-Hydroxy-ethyl)-nicotinamide (3.3 g, 20.0 mmol, 1.0 eq.) was dissolved in DCM (100 mL) and pyridine (20 mL). The light yellow solution was cooled to 2° C. A solution of 4-phenylbutanoylchloride (3.65 g of 20 mmol, 1.0 eq.) in DCM (25 mL) was slowly added. The reaction mixture was stirred for 1 h at 0° C. The reaction mixture was evaporated under reduced pressure and the residue was dissolved in water (100 mL) and ethyl acetate (100 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (75 mL). The combined organic layers were washed with a saturated aqueous solution of NaHCO3 (50 mL) and of brine (50 mL). The organic layer was dried over Na2SO4, filtrated and evaporated under reduced pressure. The yellow, oily residue was dried at high vacuum at room temperature to give 6.2 g (100%) of the product as yellow oil. The crude product was purified by flash chromatography over silica gel with ethyl acetate to yield the pure 4-phenyl-butyric acid 2-[(pyridine-3-carbonyl)amino]-ethyl ester 5.6 g (89%) as a light yellow oil. 1H NMR (CDCl3) δ=1.87-1.95 (m, 2H), 2.29-2.34 (m, 2H), 2.58-2.63 (m, 2H), 3.67-3.72 (m, 2H), 4.25-4.29 (m, 2H), 7.11-7.41 (m, 7H), 8.08-8.12 (m, 1H), 8.65-8.67 (q, 1H), 8.99-9.00 (d, 1H). 13C NMR (CDCl3) δ=26.3, 33.4, 35.0, 39.6, 62.9, 123.5, 126.0, 128.4, 128.4, 130.0, 135.2, 141.1, 148.1, 152.1, 165.8, 173.9. MS (ESI) m/z=313.2 (100) [M+H+]. DC (silica gel/ethyl acetate): RF=0.32.

Workup

  1. customThe reaction mixture was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in water (100 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate (75 mL)
  5. washThe combined organic layers were washed with a saturated aqueous solution of NaHCO3 (50 mL) and of brine (50 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltrated
  8. customevaporated under reduced pressure
  9. customThe yellow, oily residue was dried at high vacuum at room temperature

Sources & evidence

ORD record
ord-635d04933d80460a875d3e4c82b8d642
Source dataset
uspto-grants-2012_03
Patent number
US08129562B2

Reaction notes

Loading…