Aluminium lithium hydride → 1,1-Dimethylethyl 5-(3-hydroxy-1-propen-1-yl)-1H-indole-1-carboxylate

HRID 2361899Notes

Reaction equation

HRID 2361899 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]=[CH:18][C:19](OC)=[O:20])=[CH:14][CH:15]=2)[CH:10]=[C:9]1C)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]=[CH:18][CH2:19][OH:20])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 66891196HCID 66891196, compound

Product 1

HCID 668912231,1-Dimethylethyl 5-(3-hydroxy-1-propen-1-yl)-1H-indole-1-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of methyl 5-(2-methoxycarbonyl-vinyl)-indole-1-carboxylic acid tert-butyl ester (4.64 g, 15.3 mmol, 1.0 eq.) in THF (87 mL) at −30° C. was added LiAlH4 (1 N in THF, 18.6 mL, 1.2 eq.) by syringe pump over 20 min and the resulting mixture was stirred and warmed to −5° C. After cooling back to −30° C., the reaction was then quenched by slow addition of acetone (10 mL) keeping temperature below −15° C., poured into Rochelle salt at 0° C., stirred for 1 h and the separated aqueous layer was extracted with EtOAc. The combunede organic phase was dried over sodium sulfate, filtered and concentrated. The residue was purification by column chromatography (methylene chloride to 2% acetone/methylene chloride) to give 5-(3-hydroxy-propenyl)-indole-1-carboxylic acid tert-butyl ester (2.89 g, 70%) or similarly 6-(3-hydroxy-propenyl)-indole-1-carboxylic acid tert-butyl ester.

Workup

  1. temperatureAfter cooling back to −30° C.
  2. customthe reaction was then quenched by slow addition of acetone (10 mL)
  3. customtemperature below −15° C.
  4. additionpoured into Rochelle salt at 0° C.
  5. stirringstirred for 1 h
  6. extractionthe separated aqueous layer was extracted with EtOAc
  7. dry with materialThe combunede organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurification by column chromatography (methylene chloride to 2% acetone/methylene chloride)

Sources & evidence

ORD record
ord-4b8da22be5464e6c99e1ef8dc6613d51
Source dataset
uspto-grants-2014_04
Patent number
US08691814B2

Reaction notes

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