Hydrochloric Acid → tert-Butyl 3-{4-bromo-3-[isobutyryl-(2-triisopropylsilanyloxyethyl)amino]benzyloxy}-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

HRID 1712377Notes

Reaction equation

HRID 1712377 reaction equation
[Br:1][C:2]1[CH:42]=[CH:41][C:5]([CH2:6][O:7][CH:8]2[CH:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[O:32][CH3:33])=[CH:16][CH:15]=3)[CH2:12][CH2:11][N:10]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:9]2)=[CH:4][C:3]=1[NH:43][C:44](=[O:48])[CH:45]([CH3:47])[CH3:46].[H-].[Na+].I[CH2:52][CH2:53][O:54][Si:55]([CH:62]([CH3:64])[CH3:63])([CH:59]([CH3:61])[CH3:60])[CH:56]([CH3:58])[CH3:57].Cl>CN(C)C=O>[Br:1][C:2]1[CH:42]=[CH:41][C:5]([CH2:6][O:7][CH:8]2[CH:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[O:32][CH3:33])=[CH:16][CH:15]=3)[CH2:12][CH2:11][N:10]([C:34]([O:36][C:37]([CH3:39])([CH3:40])[CH3:38])=[O:35])[CH2:9]2)=[CH:4][C:3]=1[N:43]([C:44](=[O:48])[CH:45]([CH3:46])[CH3:47])[CH2:52][CH2:53][O:54][Si:55]([CH:59]([CH3:60])[CH3:61])([CH:56]([CH3:58])[CH3:57])[CH:62]([CH3:63])[CH3:64]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 11450272(2-Iodoethoxy)triisopropylsilaneHCID 68500125Tert-butyl 3-(4-bromo-3-isobutyrylaminobenzyloxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

Product 1

HCID 86609997tert-Butyl 3-{4-bromo-3-[isobutyryl-(2-triisopropylsilanyloxyethyl)amino]benzyloxy}-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The solution of 3.50 g of tert-butyl 3-(4-bromo-3-isobutyrylaminobenzyloxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate in 25 ml of N,N-dimethylformamide is cooled to 0° C. with stirring and admixed with sodium hydride dispersion (60%). After 30 minutes, the mixture is admixed with 1.66 g of (2-iodoethoxy)triisopropylsilane and stirred at room temperature over 16 hours. The reaction mixture is admixed with cold 1N HCl (100 ml) and extracted with tert-butyl methyl ether (2×100 ml). The organic phases are washed successively with water (100 ml) and brine (100 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rt=7.60.

Workup

  1. stirringstirred at room temperature over 16 hours
  2. extractionextracted with tert-butyl methyl ether (2×100 ml)
  3. washThe organic phases are washed successively with water (100 ml) and brine (100 ml)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-c21b4fdb970b4c3f98f772b4757dae78
Source dataset
uspto-grants-2010_09
Patent number
US07790715B2

Reaction notes

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