1-Chloro-4-(chloromethyl)benzene → 4-{2-[3-(1-tert-Butoxycarbonylmethyl-piperidin-4-yl)-1-(4-chloro-benzyl)-1H-indazol-6-yl]-(E)-vinyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 343411Notes

Reaction equation

HRID 343411 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](/[CH:14]=[CH:15]/[C:16]2[CH:24]=[C:23]3[C:19]([C:20]([CH:25]4[CH2:30][CH2:29][N:28]([CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27][CH2:26]4)=[N:21][NH:22]3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:41][C:42]1[CH:49]=[CH:48][C:45]([CH2:46]Cl)=[CH:44][CH:43]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](/[CH:14]=[CH:15]/[C:16]2[CH:24]=[C:23]3[C:19]([C:20]([CH:25]4[CH2:26][CH2:27][N:28]([CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:30]4)=[N:21][N:22]3[CH2:46][C:45]3[CH:48]=[CH:49][C:42]([Cl:41])=[CH:43][CH:44]=3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 178451206HCID 178451206, compound

Product 1

HCID 700971444-{2-[3-(1-tert-Butoxycarbonylmethyl-piperidin-4-yl)-1-(4-chloro-benzyl)-1H-indazol-6-yl]-(E)-vinyl}-piperidine-1-carboxylic acid tert-butyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 4-{2-[3-(1-tert-butoxycarbonylmethyl-piperidin-4-yl)-1H-indazol-6-yl]-(E)-vinyl}-piperidine-1-carboxylic acid tert-butyl ester (0.29 g, 0.553 mmol) in dry DMF (5 ml) was stirred under nitrogen and treated with sodium hydride (0.024 g, 0.608 mmol, 60% dispersion in oil). The mixture was stirred for 0.5 h and a solution of 4-chlorobenzyl chloride (0.090 g, 0.559 mmol; Aldrich) in DMF (5 ml) was added). The mixture was stirred at 23° for 16 h, evaporated in vacuo, treated with water (10 ml) and extracted with dichloromethane (3×20 ml). The extracts were evaporated in vacuo and purified by flash chromatography on silica gel (Merck 9385), eluant ether:cyclohexane:triethylamine (50:50:2 to 100:0:2), to give the title compound as a colourless gum (0.157 g, 44%).

Workup

  1. stirringThe mixture was stirred at 23° for 16 h
  2. customevaporated in vacuo
  3. additiontreated with water (10 ml)
  4. extractionextracted with dichloromethane (3×20 ml)
  5. customThe extracts were evaporated in vacuo
  6. custompurified by flash chromatography on silica gel (Merck 9385), eluant ether:cyclohexane:triethylamine (50:50:2 to 100:0:2)

Sources & evidence

ORD record
ord-e703495db6a6498f80b9238cce4c5399
Source dataset
uspto-grants-1999_01
Patent number
US05861414

Reaction notes

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