Methanol → tert-butyl 3-formyl-1H-indole-1-carboxylate

HRID 742549Notes

Reaction equation

HRID 742549 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1.[OH-].[K+].[C:14]([O:18][C:19](=O)[O:20]C(C)(C)C)([CH3:17])([CH3:16])[CH3:15].CO>O1CCCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:14]([O:18][C:19]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 887MethanolHCID 10256Indole-3-CarboxaldehydeHCID 14797Potassium HydroxideHCID 10219638Carbonic acid, bis(1,1-dimethylethyl) ester

Product 1

HCID 2764519tert-butyl 3-formyl-1H-indole-1-carboxylateYield 97.7%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Indole-3-carboxaldehyde (4.53 g, 30 mmol) was dissolved in tetrahydrofuran (100 mL) (dissolved at about 40° C.). Aqueous potassium hydroxide (1N, 30 mL) and tetrabutylammonium bromide (0.97 g, 3 mmol) were added. Then di-t-butylcarbonate (7.2 g, 33 mmol) was added (the temperature should not rise about 25° C.). The resulting mixture was stirred at room temperature until the starting material was not detected by TLC (CH2CL2 /CH3OH 9:1). The reaction mixture was separated, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layer was dried with MgSO4 and evaporated to give crude product. The product was recrystallized from methylene chloride/hexane (20 mL/100 mL) to obtain needle crystals (7.19 g, 97.7%). m.p. 124°-125° C.

Workup

  1. customrise about 25° C.
  2. customThe reaction mixture was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  4. dry with materialThe combined organic layer was dried with MgSO4
  5. customevaporated
  6. customto give crude product
  7. customThe product was recrystallized from methylene chloride/hexane (20 mL/100 mL)

Sources & evidence

ORD record
ord-f0f7f88b04d849639ce0fc1e38814c03
Source dataset
uspto-grants-1996_09
Patent number
US05554753

Reaction notes

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