Phenylacetyl chloride → Ethyl 5-Chloro-2-(phenylacetamido)nicotinate

HRID 2392722Notes

Reaction equation

HRID 2392722 reaction equation
[C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:11][C:12]1[N:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:13]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15]>N1C=CC=CC=1>[Cl:23][C:20]1[CH:21]=[N:22][C:12]([NH:11][C:8](=[O:9])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[C:13]([CH:19]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

4

Reactant 2

HCID 7679Phenylacetyl chlorideHCID 18980364Ethyl 2-amino-5-chloronicotinate

Product 1

HCID 53698644Ethyl 5-Chloro-2-(phenylacetamido)nicotinate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
130 °C

Procedure

Phenylacetyl chloride (0.21 mL, d=1.169, 1.6 mmol) was added to ethyl 2-amino-5-chloronicotinate (143) (159.6 mg, 0.7956 mmol) in a 10 mL round-bottom flask. A stir bar and pyridine (1.0 mL, distilled) were added. The mixture was heated to reflux (130° C., oil bath) with stirring under nitrogen. The resulting solution was refluxed for 1 h, then cooled to room temperature. The reaction mixture was quenched with water (5 mL) and extracted with chloroform (3×10 mL). The combined organic extracts were washed with sat. NaHCO3 (3×10 mL) and water (3×10 mL), dried (MgSO4), and rota-evaporated to dryness, leaving an orange liquid. This liquid was chromatographed on silica gel (30 g, Mallinckrodt, grade 62, mesh 60-200) and eluded with hexanes-EtOAc (1:4, 250 mL). The desired fractions were collected (Rf =0.79) and rota-evaporated to dryness, leaving an orange solid. Crystallization from ethanol afforded the title compound as yellow needles, 110 mg (43.6%), mp 113.5°-114° C.; 1H NMR (CDCl3): δ1.38 (t, J=7.2, 3, CH3CH2), 3.90 (s, 2, benzylic), 4.34 (q, J=7.2, 2, CH3CH2O), 7.38 (m, 5, phenyl), 8.22 (d, J=2.4, 1, py), 8.54 (d, J=2.4, 1, py), 10.64 (s, 1, NH); IR (KBr): 3427, 3196, 1743, 1640, 1600, 1409, 1272, 1218, 1136, 1096, 796; HPLC: 100%; LRMS: 318 (M+, 25), 202 (20), 201 (10), 200 (60), 183 (15), 181 (40), 154 (10), 128 (10), 118 (100 ), 91 (80), 65 (25), 39 (10); HRMS Calcd: 318.0771. Found: 318.0772.

Workup

  1. temperatureThe mixture was heated
  2. temperatureThe resulting solution was refluxed for 1 h
  3. temperaturecooled to room temperature
  4. customThe reaction mixture was quenched with water (5 mL)
  5. extractionextracted with chloroform (3×10 mL)
  6. washThe combined organic extracts were washed with sat. NaHCO3 (3×10 mL) and water (3×10 mL)
  7. dry with materialdried (MgSO4)
  8. customrota-evaporated to dryness
  9. customleaving an orange liquid
  10. customThis liquid was chromatographed on silica gel (30 g, Mallinckrodt, grade 62, mesh 60-200)
  11. customThe desired fractions were collected (Rf =0.79)
  12. customrota-evaporated to dryness
  13. customleaving an orange solid
  14. customCrystallization from ethanol

Sources & evidence

ORD record
ord-c69f6e16905c49eeb96a7d14097d23fe
Source dataset
uspto-grants-1998_09
Patent number
US05801183

Reaction notes

Loading…