Pivaloyl chloride → Methyl 3-[N-(4-chlorobenzyl)-3-(1,1-dimethylethyl)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate

HRID 327255Notes

Reaction equation

HRID 327255 reaction equation
[CH3:1][C:2](C)([CH3:6])[C:3](Cl)=O.[Al+3].[Cl-].[Cl-].[Cl-].[Cl:12][C:13]1[CH:48]=[CH:47][C:16]([CH2:17][N:18]2[C:26]3[C:21](=[CH:22][C:23]([O:27][CH2:28][C:29]4[CH:38]=[CH:37][C:36]5[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=5)[N:30]=4)=[CH:24][CH:25]=3)[CH:20]=[C:19]2[CH2:39][C:40]([CH3:46])([CH3:45])[C:41]([O:43][CH3:44])=[O:42])=[CH:15][CH:14]=1.C(C(C(C([O-])=O)O)O)([O-])=O>C(Cl)Cl.CCOC(C)=O>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][N:18]2[C:26]3[C:21](=[CH:22][C:23]([O:27][CH2:28][C:29]4[CH:38]=[CH:37][C:36]5[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=5)[N:30]=4)=[CH:24][CH:25]=3)[C:20]([C:2]([CH3:6])([CH3:3])[CH3:1])=[C:19]2[CH2:39][C:40]([CH3:45])([CH3:46])[C:41]([O:43][CH3:44])=[O:42])=[CH:47][CH:48]=1

Participants

7

Reactant 4

HCID 62493Pivaloyl chlorideHCID 38061142,3-DihydroxybutanedioateHCID 6451240Aluminum(III) ChlorideHCID 9892642Methyl 3-[N-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate

Product 1

HCID 18947566Methyl 3-[N-(4-chlorobenzyl)-3-(1,1-dimethylethyl)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Trimethylacetyl-chloride (4.23 g, 4.32 mL, 35.09 mmol) was added to a cold suspension (0° C.) of AlCl3 (11.7 g, 87.7 mmol) in dry CH2Cl2 (60 mL) under Ar. The yellow mixture was stirred at 0° C. for 15 minutes, and a solution of 9.00 g (17.54 mmol) of methyl 3-[N-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate (prepared in Step A) in CH2Cl2 (40 mL) was added dropwise (over 10 minutes) at 0° C. The reaction mixture was stirred for 10 minutes and slowly poured onto an ice-cold and vigourously stirred mixture of 0.5M aqueous Na, K tartrate (500 mL) and EtOAc (400 mL). After 20 minutes, the aqueous layer was extracted with EtOAc (2×) and the combined organic extracts were washed with H2O (2×), with IN aqueous NaOH (2×), with H2O (2×) and dried (MgSO4). Filtration and removal of solvents provided a yellow oily residue which was chromatographed on silica gel using EtOAc-hexane (1:4) to give the title compound.

Workup

  1. stirringThe reaction mixture was stirred for 10 minutes
  2. waitAfter 20 minutes
  3. extractionthe aqueous layer was extracted with EtOAc (2×)
  4. washthe combined organic extracts were washed with H2O (2×), with IN aqueous NaOH (2×), with H2O (2×)
  5. dry with materialdried (MgSO4)
  6. filtrationFiltration and removal of solvents
  7. customprovided a yellow oily residue which
  8. customwas chromatographed on silica gel

Sources & evidence

ORD record
ord-45ca19ed8d1e4418a502ba0faf1c1284
Source dataset
uspto-grants-1993_12
Patent number
US05272145

Reaction notes

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