Formic Acid → 3-Methyl-2,3-dihydro-1H-indole-1-carbaldehyde

HRID 2099552Notes

Reaction equation

HRID 2099552 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[CH:10]([OH:12])=O.O.[C:14]1(C)C=CC=CC=1>>[CH3:14][CH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]([CH:10]=[O:12])[CH2:2]1

Participants

5

Reactant 4

HCID 284Formic AcidHCID 962WaterHCID 1140TolueneHCID 10328Indoline

Product 1

HCID 127981573-Methyl-2,3-dihydro-1H-indole-1-carbaldehyde

Procedure

Indoline (23.3 g, 175 mmol) with formic acid (11.5 ml, 305 mmol) was refluxed in toluene (250 mL) with a Dean-Stark trap to collect the formed water. After 1 h of reflux, 6 mL of water was tapped off and the reaction mixture was cooled to RT, some greenish solid was formed in the mixture. Water (250 mL) was added and the organic layer was washed with another portion of water (250 mL) and with brine (250 mL), dried over Na2SO4, filtered and evaporated to dryness. Yield: 22.5 g (80% of a yellow oil, identified as 3 by 1H-NMR. This crude material was crystallized from 2-propanol, the formed crystals were collected by filtration and washed with 2-propanol. Yield: 3.0 g (11%). The mother liquor was evaporated to dryness and the residue was purified by column chromatography (Silica, EtOAc: heptanes=1:3→1:1). Yield: 15.5 g (55%) of a yellowish oil that crystallized upon standing. The two portions were combined and used as such in the next step.

Workup

  1. customto collect the formed water
  2. temperatureAfter 1 h of reflux
  3. customsome greenish solid was formed in the mixture
  4. washthe organic layer was washed with another portion of water (250 mL) and with brine (250 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThis crude material was crystallized from 2-propanol
  9. filtrationthe formed crystals were collected by filtration
  10. washwashed with 2-propanol
  11. customThe mother liquor was evaporated to dryness
  12. customthe residue was purified by column chromatography (Silica, EtOAc: heptanes=1:3→1:1)
  13. customYield: 15.5 g (55%) of a yellowish oil that crystallized

Sources & evidence

ORD record
ord-40f58f5e6b8e434f85f00d41c8acb170
Source dataset
uspto-grants-2009_08
Patent number
US07569604B2

Reaction notes

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