Hydrochloric Acid → Lithium diisopropylamide

HRID 74478Notes

Reaction equation

HRID 74478 reaction equation
C([Li:5])CCC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Cl:13][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[CH:16]=[CH:17][N:18]2[S:23]([C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1)(=[O:25])=[O:24].Cl[C:34]([O:36][CH3:37])=[O:35].Cl>O1CCCC1.CCCCCC>[CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Li+:5].[CH3:37][O:36][C:34]([C:17]1[N:18]([S:23]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:19]2[C:15]([CH:16]=1)=[C:14]([Cl:13])[CH:22]=[CH:21][CH:20]=2)=[O:35]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 7912DiisopropylamineHCID 116236834-Chloro-1-((4-methylphenyl)sulfonyl)-1H-indoleHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 680050964-chloro-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A lithium diisopropyl amide solution was prepared by adding, at −78° C., a hexane solution of 1.0 M n-butyl lithium to an anhydrous tetrahydrofuran (THF) solution (1.5 ml) of diisopropyl amine (370 μl). The prepared solution was added at −78° C. to a tetrahydrofuran (THF) solution (6 ml) of 4-chloro-1-(toluene-4-sulfonyl)-1H-indole. This was stirred for 15 minutes. After adding methyl chloroformate (169 μl) thereto, the reaction mixture was stirred at −78° C. for 15 minutes, and then an aqueous solution (4 ml) of 1 M hydrochloric acid was added thereto at −78° C. After warming it to room temperature, the reaction mixture was extracted with ethyl acetate (10 ml). The organic layer was washed with an aqueous solution saturated with sodium chloride, and the organic layer was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate). Thus, 4-chloro-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid methyl ester was obtained as a colorless solid (591 mg, 82%).

Workup

  1. additionby adding, at −78° C.
  2. stirringthe reaction mixture was stirred at −78° C. for 15 minutes
  3. customat −78° C
  4. extractionthe reaction mixture was extracted with ethyl acetate (10 ml)
  5. washThe organic layer was washed with an aqueous solution saturated with sodium chloride
  6. concentrationthe organic layer was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c095b5b546854043902eccadba976898
Source dataset
uspto-grants-2014_09
Patent number
US08829199B2

Reaction notes

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