Toluene → ethyl 2-hydroxy-2-(1-phenyl-1H-indol-2-yl)acetate

HRID 590967

Reaction equation

HRID 590967 reaction equation
C([Li])CCC.[C:6]1([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:21]([O:25][CH2:26][CH3:27])(=[O:24])[CH:22]=[O:23].C1(C)C=CC=CC=1>O1CCCC1>[OH:23][CH:22]([C:13]1[N:12]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:20]2[C:15]([CH:14]=1)=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:21]([O:25][CH2:26][CH3:27])=[O:24]

Participants

6

Reactant 4

HCID 1140TolueneHCID 70211Ethyl oxoacetateHCID 1820291-Phenyl-1H-indoleHCID 178418339Butyllithium

Product 1

HCID 70813712ethyl 2-hydroxy-2-(1-phenyl-1H-indol-2-yl)acetateYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of butyllithium (1.6 M, 1.19 mL, 1.9 mmol) was added at −78° C. to a solution of 1-phenyl-1H-indole (5a) (350 mg, 1.81 mmol) in tetrahydrofuran (10 mL) under a nitrogen atmosphere. After 45 minutes, a solution of ethyl glyoxylate in toluene (50%, 400 μL, 2 mmol) was added. The reaction mixture was slowly warmed to room temperature for 12 hours, quenched with water (2 mL) and concentrated in vacuo. The residue was partitioned between dichloromethane (30 mL) and water (10 mL). The organic layer was washed with water (2×10 mL), brine (10 mL), dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 90/10) to afford the desired alcohol (5b) as a white solid (100 mg, 0.33 mmol, 19%).

Workup

  1. customquenched with water (2 mL)
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between dichloromethane (30 mL) and water (10 mL)
  4. washThe organic layer was washed with water (2×10 mL), brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 90/10)

Sources & evidence

ORD record
ord-e651d3765b184ad7b428914d243b832a
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Linked notes

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