Imidazole → 4-((alphaS)-alpha-((2R,5R)-2,5-dimethyl-4-propyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)-N,N-diethylbenzamide

HRID 538270Notes

Reaction equation

HRID 538270 reaction equation
[CH2:1]([N:4]1[C@H:9]([CH3:10])[CH2:8][N:7]([C@@H:11]([C:19]2[CH:31]=[CH:30][C:22]([C:23]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[O:24])=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([OH:18])[CH:13]=2)[C@H:6]([CH3:32])[CH2:5]1)[CH:2]=[CH2:3].C1(O)C=CC=CC=1.[C:40]([Si:44](Cl)([CH3:46])[CH3:45])([CH3:43])([CH3:42])[CH3:41].N1C=CN=C1>C1(C)C=CC=CC=1.C(#N)C.O>[CH3:32][C@@H:6]1[CH2:5][N:4]([CH2:1][CH2:2][CH3:3])[C@H:9]([CH3:10])[CH2:8][N:7]1[C@@H:11]([C:19]1[CH:20]=[CH:21][C:22]([C:23]([N:25]([CH2:26][CH3:27])[CH2:28][CH3:29])=[O:24])=[CH:30][CH:31]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][Si:44]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:46])[CH3:45])[CH:13]=1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 996PhenolHCID 28928tert-Butyldimethylsilyl chlorideHCID 10238234HCID 10238234, compound

Product 1

HCID 186650764-((alphaS)-alpha-((2R,5R)-2,5-dimethyl-4-propyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)-N,N-diethylbenzamideYield 33.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

(−)-4-((αS)-α-((2R,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (0.200 g, 0.46 mmol, Example 2) was dissolved in toluene (10 mL) and stirred for 4 hours under a hydrogen atmosphere. The solution was filtered through celite to give 0.182 g of crude product. The phenol was reprotected as follows to improve chromatographic resolution. A mixture of crude product (0.18 g), tert-butylchlorodimethylsilane (0.93 g), and imidazole (0.070 g) in 10 mL of acetonitrile was stirred overnight at room temperature. The reaction solution was poured into 100 mL of water and extracted with two 50 mL portions of dichloromethane. The combined extracts were dried over sodium sulfate and the solvent removed. The residue was purified on a column of silica gel with ethanol (0-4%) in dichloromethane to give 0.085 g of 4-((αS)-α-((2R,5R)-2,5-dimethyl-4-propyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)-N,N-diethylbenzamide as a light-brown solid.

Workup

  1. filtrationThe solution was filtered through celite
  2. customto give 0.182 g of crude product
  3. stirringwas stirred overnight at room temperature
  4. extractionextracted with two 50 mL portions of dichloromethane
  5. dry with materialThe combined extracts were dried over sodium sulfate
  6. customthe solvent removed
  7. customThe residue was purified on a column of silica gel with ethanol (0-4%) in dichloromethane

Sources & evidence

ORD record
ord-a2a5002161bd4157aa9978c80a7c4e93
Source dataset
uspto-grants-2014_10
Patent number
US08865721B2

Reaction notes

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