Sodium Hydroxide → Methyl 3-[3-(4-chlorobenzyl)-6-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate

HRID 327248Notes

Reaction equation

HRID 327248 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10](=O)[CH2:11][C:12]([CH3:18])([CH3:17])[C:13]([O:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.[N:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][C:21]=1[CH2:30][O:31][C:32]1[CH:33]=[C:34]([NH:38]N)[CH:35]=[CH:36][CH:37]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.CC(O)=O.CCOCC.ClCCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:35]3[C:34](=[CH:33][C:32]([O:31][CH2:30][C:21]4[CH:22]=[CH:23][C:24]5[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=5)[N:20]=4)=[CH:37][CH:36]=3)[NH:38][C:10]=2[CH2:11][C:12]([CH3:18])([CH3:17])[C:13]([O:15][CH3:16])=[O:14])=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 14798Sodium HydroxideHCID 18947527Methyl 6-(4-chlorophenyl)-2,2-dimethyl-4-oxohexanoateHCID 189475383-(Quinolin-2-ylmethoxy)phenylhydrazine

Product 1

HCID 18947534Methyl 3-[3-(4-chlorobenzyl)-6-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of methyl 6-(4-chlorophenyl)-2,2-dimethyl-4-oxohexanoate (Step C, 2.8 g) in toluene (30 mL) and glacial HOAc (15 mL) was added portion-wise solid 3-(quinolin-2-ylmethoxy)-phenylhydrazine (Step A, 3.2 g) and stirred at room temperature for 2 hours. The reaction mixture was diluted with Et2O (200 mL), washed with 1N NaOH, H2O, dried (Na2SO4) and evaporated to give crude hydrazone which was immediately treated as follows: the crude hydrazone was dissolved in a mixture of PPE(15 mL) and 1,2-dichloroethane (30 mL) and stirred at 40° C. for 18 hours. The reaction mixture was cooled to 0° C. and carefully treated with 1N NaOH to bring to pH 9. The mixture was then extracted with ether, the extract was washed with H2O, dried (Na2SO4) and evaporated to give a residue, which was chromatographed in a column of flash silica gel (eluting with EtOAc-hexane 25:75) and isolating the most polar component as the title product as a foam.

Workup

  1. washwashed with 1N NaOH, H2O
  2. dry with materialdried (Na2SO4)
  3. customevaporated
  4. customto give crude hydrazone which
  5. additionwas immediately treated
  6. stirringstirred at 40° C. for 18 hours
  7. temperatureThe reaction mixture was cooled to 0° C.
  8. extractionThe mixture was then extracted with ether
  9. washthe extract was washed with H2O
  10. dry with materialdried (Na2SO4)
  11. customevaporated
  12. customto give a residue, which
  13. customwas chromatographed in a column of flash silica gel (eluting with EtOAc-hexane 25:75)

Sources & evidence

ORD record
ord-446fcc6ab5c94ce39da226d4f26ea92d
Source dataset
uspto-grants-1993_12
Patent number
US05272145

Reaction notes

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