Dimethylformamide → Methyl 3-formyl-1H-indole-5-carboxylate

HRID 1851951Notes

Reaction equation

HRID 1851951 reaction equation
O=P(Cl)(Cl)Cl.[NH:6]1[C:14]2[C:9](=[CH:10][C:11]([C:15]([O:17][CH3:18])=[O:16])=[CH:12][CH:13]=2)[CH:8]=[CH:7]1.CN([CH:22]=[O:23])C>>[CH:22]([C:8]1[C:9]2[C:14](=[CH:13][CH:12]=[C:11]([C:15]([O:17][CH3:18])=[O:16])[CH:10]=2)[NH:6][CH:7]=1)=[O:23]

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 2737635methyl 1H-indole-5-carboxylate

Product 1

HCID 19606277Methyl 3-formyl-1H-indole-5-carboxylateYield 91%

Conditions

Temperature
0 °C

Procedure

To a solution of anhydrous DMF (12 mL) under argon at 0° C. was added POCl3 (446 μL, 4.9 mmol). The reaction mixture has been stirred at 0° C. for 5 min. The methyl 1H-indole-5-carboxylate (854 mg, 4.9 mmol) in solution in DMF was added dropwise. The resulting mixture has been heated at 120° C. for 1 h. Then, it is quenched by addition of a saturated solution of NaHCO3 (2 mL). The mixture is diluted with DCM, washed with brine, dried over MgSO4 and concentrated. The product is precipitated in hexane/diethyl ether (1/1) to yield a red powder (896 mg, 4.4 mmol, 91%). ESI-MS (m/z): 204 [M+H]+.

Workup

  1. temperatureThe resulting mixture has been heated at 120° C. for 1 h
  2. customThen, it is quenched by addition of a saturated solution of NaHCO3 (2 mL)
  3. additionThe mixture is diluted with DCM
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe product is precipitated in hexane/diethyl ether (1/1)

Sources & evidence

ORD record
ord-b6fdf3b35b3b41f0b642e924eb5dac6c
Source dataset
uspto-grants-2015_02
Patent number
US08957093B2

Reaction notes

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