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Hydrochloric Acid → Ethyl 3-[1-(p-bromobenzyl)-5-methoxy-2-methylindol-3-yl]-4,4,4-trifluorobutanoat

HRID 1451527
Notes
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Reaction equation

HRID 1451527 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[CH:13]([C:20]([F:23])([F:22])[F:21])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Br:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39]Br)=[CH:37][CH:36]=1.Cl>C1COCC1>[Br:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39][N:8]2[C:9]3[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=3)[C:6]([CH:13]([C:20]([F:23])([F:22])[F:21])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:7]2[CH3:12])=[CH:37][CH:36]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 685274-Bromobenzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 19974941Ethyl 3-(5-methoxy-2-methylindol-3-yl)-4,4,4-trifluorobutanoate

Product 1

HCID 19974932Ethyl 3-[1-(p-bromobenzyl)-5-methoxy-2-methylindol-3-yl]-4,4,4-trifluorobutanoatYield 64%

Reagents, catalysts & solvents

1
HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a -78° C. solution of the indole from Step 3 (3.1 g, 9.4 mmol) in 65 mL of THF was added KHMDS (0.6M toluene solution, 18.8 mL, 11.3 mmol) dropwise. The solution was warmed to 0° C., then cooled to -78° C. A solution of p-bromobenzyl bromide (3.0 g, 12.2 mmol) was then added, and the solution was allowed to warm to room temperature. The solution was then poured into 1M HCl and extracted with ether. The organic extracts were washed with brine, dried over MgSO4 and evaporated. The residue was purified by flash chromatography (20% ethyl acetate/hexanes) to provide 3.0 g of the title compound.

Workup

  1. temperaturecooled to -78° C
  2. temperatureto warm to room temperature
  3. extractionextracted with ether
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe residue was purified by flash chromatography (20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ea5fb29cbd5944c0a7f547a1785b3b58
Source dataset
uspto-grants-1997_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05604253

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes