Methyl iodide → tert-Butyl 3-(2-{2-[2-(acetylmethylamino)ethyl]phenoxy}ethoxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

HRID 1712290Notes

Reaction equation

HRID 1712290 reaction equation
C([NH:4][CH2:5][CH2:6][C:7]1[CH:49]=[CH:48][CH:47]=[CH:46][C:8]=1[O:9][CH2:10][CH2:11][O:12][CH:13]1[CH:18]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[O:37][CH3:38])=[CH:21][CH:20]=2)[CH2:17][CH2:16][N:15]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:14]1)(=O)C.[H-].[Na+].CI>CN(C)C=O>[C:8]([CH2:46][NH:4][CH2:5][CH2:6][C:7]1[CH:49]=[CH:48][CH:47]=[CH:46][C:8]=1[O:9][CH2:10][CH2:11][O:12][CH:13]1[CH:18]([C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][CH2:28][O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[O:37][CH3:38])=[CH:23][CH:24]=2)[CH2:17][CH2:16][N:15]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:14]1)(=[O:9])[CH3:7]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68505604tert-Butyl 3-{2-[2-(2-acetylaminoethyl)phenoxy]ethoxy}-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

Product 1

HCID 68506023tert-Butyl 3-(2-{2-[2-(acetylmethylamino)ethyl]phenoxy}ethoxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

A solution of 0.099 g of tert-butyl 3-{2-[2-(2-acetylaminoethyl)phenoxy]ethoxy}-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate (Example 14a) in 3 ml of N,N-dimethylformamide is admixed with stirring at room temperature with 0.023 g of sodium hydride dispersion (55%). After 30 minutes at room temperature, a solution of 0.055 ml of methyl iodide in 0.4 ml of N,N-dimethylformamide is added dropwise. The reaction mixture is stirred at 75° C. over 18 hours, cooled, poured onto water and extracted with tertbutyl methyl ether (2×). The combined organic phases are dried with sodium sulphate and concentrated by evaporation. The title compound is obtained as a yellow oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.09 (1.5:1 EtOAc-heptane); Rt=5.84.

Workup

  1. temperaturecooled
  2. additionpoured onto water
  3. extractionextracted with tertbutyl methyl ether (2×)
  4. dry with materialThe combined organic phases are dried with sodium sulphate
  5. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-7848bbe16f544052820b86f12e54403b
Source dataset
uspto-grants-2010_09
Patent number
US07790715B2

Reaction notes

Loading…