Water → N-Ethyl-4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperidinecarboxamide

HRID 260713Notes

Reaction equation

HRID 260713 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH2:10][CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.[CH2:17]([N:19]=[C:20]=[O:21])[CH3:18].O>ClCCl>[CH2:17]([NH:19][C:20]([N:14]1[CH2:13][CH2:12][CH:11]([CH2:10][C:3]2[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=2[F:1])[CH2:16][CH2:15]1)=[O:21])[CH3:18]

Participants

5

Reactant 3

HCID 962WaterHCID 8022Ethyl isocyanateHCID 158395224-[(2-Fluoro-5-methoxyphenyl)methyl]piperidine

Product 1

HCID 15839521N-Ethyl-4-[(2-fluoro-5-methoxyphenyl)methyl]-1-piperidinecarboxamideYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
5 °C

Procedure

A magnetically stirred solution of 4-[(2-fluoro-5-methoxyphenyl)methyl]piperidine (0.895 g, 4.01 mmol) in anhydrous dichloromethane (15 mL) at 5° C. was treated dropwise with a solution of ethyl isocyanate (0.320 g, 4.41 mmol) in dry dichloromethane (5 mL). The solution was stirred 0.5 h at 5° C., allowed to warm to room temperature and stirred for 48 h. The solution was poured over ice (50g), and treated with water (200 mL) and dichloromethane (250 mL). The layers were separated, the aqueous phase was back-extracted with fresh dichloromethane (3×200 mL), and the combined organic portions were washed with 1N hydrochloric acid solution (350 mL), 5% sodium hydroxide solution (400 mL), water (400 mL), saturated brine (400 mL), dried is (K2CO3), filtered, and concentrated in vacuo. Drying (85° C.) in vacuo gave 1.08 g (92%) of the desired product as a clear oil: IR (film) 3346, 2930, 1622, 1592, 1538, 1498, 1274, 1252; 1214, 1036 cm-1 ; 1H NMR (CDCl3) δ6.90 (t, J=9.0 Hz, 1H), 6.69-6.60 (m, 2H), 4.50 (bt, J=4.7 Hz, 1H), 3.89 (bd, J=13.2 Hz, 2H), 3.74 (s, 3H), 3.27-3.17 (m, 2H), 2.67 (td, J=12.8, 2.4 Hz, 2H), 2.52 (dd, J=7.1, 1.1 Hz, 2H), 1.74-1.61 (m, 1H), 1.62 (bd, J=13.5 Hz, 2H), 1.18 (qd, J=12.0, 4.0 Hz, 2H), 1.10 (t, J=7.2 Hz, 3H); 13C NMR (CDCl3)δ57.7, 155.7 (d, J=237.1 Hz), 155.4 (d, J=1.7 Hz, 127.8 (d, J=18.0 Hz), 116.6 (d, J=5.1 Hz), 115.5 (d, J=24.7 Hz), 112.1 (d, J=8.0 Hz), 55.7, 44.1, 37.0, 36.2, 35.7, 31.7, 15.6; MS m/z 295 (M+ +1, free base).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 48 h
  3. customThe layers were separated
  4. extractionthe aqueous phase was back-extracted with fresh dichloromethane (3×200 mL)
  5. washthe combined organic portions were washed with 1N hydrochloric acid solution (350 mL), 5% sodium hydroxide solution (400 mL), water (400 mL), saturated brine (400 mL)
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customDrying (85° C.) in vacuo

Sources & evidence

ORD record
ord-f5e5bf9b019b45f4b550cd6c4d3183b0
Source dataset
uspto-grants-1996_06
Patent number
US05530012

Reaction notes

Loading…