3,4-Dichlorobenzyl chloride → 4-{2-[3-(1-tert-Butoxycarbonylmethyl-piperidin-4-yl)-1-(3,4-dichloro-benzyl)-1H-indazol-6-yl]-(E)-vinyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 343409Notes

Reaction equation

HRID 343409 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13](/[CH:16]=[CH:17]/[C:18]2[CH:26]=[C:25]3[C:21]([C:22]([CH:27]4[CH2:32][CH2:31][N:30]([CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29][CH2:28]4)=[N:23][NH:24]3)=[CH:20][CH:19]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[Cl:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][C:49]=1[Cl:50])[CH2:45]Cl>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13](/[CH:16]=[CH:17]/[C:18]2[CH:26]=[C:25]3[C:21]([C:22]([CH:27]4[CH2:28][CH2:29][N:30]([CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:31][CH2:32]4)=[N:23][N:24]3[CH2:45][C:44]3[CH:47]=[CH:48][C:49]([Cl:50])=[C:42]([Cl:41])[CH:43]=3)=[CH:20][CH:19]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 76093,4-Dichlorobenzyl chlorideHCID 24758Sodium hydrideHCID 178451206HCID 178451206, compound

Product 1

HCID 675942544-{2-[3-(1-tert-Butoxycarbonylmethyl-piperidin-4-yl)-1-(3,4-dichloro-benzyl)-1H-indazol-6-yl]-(E)-vinyl}-piperidine-1-carboxylic acid tert-butyl esterYield 102.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (12.2 mg; 0.304 mmol) was added to a stirred solution of 4-{2-[3-(1-tert-butoxycarbonylmethyl-piperidin-4-yl)-1H-indazol-6-yl]-(E)-vinyl} piperidine-1-carboxylic acid tert-butyl ester (145 mg; 0.276 mmol) in dry DMF (5 ml) and the mixture was stirred at 23° under nitrogen for 25 min. 3,4-Dichlorobenzyl chloride (0.043 ml, 0.304 mmol; Aldrich) was added, and the mixture was stirred at 23° for 18 h. The solvent was evaporated in vacuo and the residue partitioned between water (25 ml) and ethyl acetate (3×20 ml). The organic layers were washed with 50:50 brine: water (30 ml) and brine, dried (MgSO4) and evaporated in vacuo to give a yellow oil (193 mg). Purification by flash chromatography on silica gel (Merck 9385), eluting with ether: cyclohexane 70:30 gave the title compound as a colourless oil (117 mg; 62%).

Workup

  1. stirringthe mixture was stirred at 23° for 18 h
  2. customThe solvent was evaporated in vacuo
  3. customthe residue partitioned between water (25 ml) and ethyl acetate (3×20 ml)
  4. washThe organic layers were washed with 50:50 brine
  5. dry with materialwater (30 ml) and brine, dried (MgSO4)
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-30115e79a806473d8f803e5836da4bcf
Source dataset
uspto-grants-1999_01
Patent number
US05861414

Reaction notes

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