Dimethylformamide → HCID 89739279, compound

HRID 1527072Notes

Reaction equation

HRID 1527072 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[CH3:11][O:12][CH2:13][C:14]([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[C:18]1[CH3:26])([CH3:16])[CH3:15]>ClCCl>[CH3:11][O:12][CH2:13][C:14]([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([CH:3]=[O:4])=[C:18]1[CH3:26])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 117779445HCID 117779445, compound

Product 1

HCID 89739279HCID 89739279, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2 ml anhydrous N,N-dimethylformamide dissolved in 80 ml anhydrous dichloromethane was added phosphoryl trichloride (5 g, 32.6 mmol) at 0° C. The resultant reaction mixture was allowed to stirred at 0° C. for 3 hours. 1-(1-methoxy-2-methylpropan-2-yl)-2-methyl-1H-indole (800 mg, 3.7 mmol) was added dropwise at 0° C. Then the resulting reaction mixture was allowed to stir for 1 hour at 0° C., and then warmed to the ambient temperature. The reaction mixture was allowed to stir for 24 hours at room temperature. The reaction mixture was quenched with saturated sodium acetate. The pH was adjusted to around 8 by progressively adding 2N sodium hydroxide below 0° C., extracted with dichloromethane (100 mL×3). The combined organic phase was dried by anhydrous sodium sulphate, and then filtered. The filtrate was concentrated and purified by column chromatograph on silica gel eluted with (petrol ether/acetic ester 10:1→5:1→2:1) to give 1-(1-methoxy-2-methylpropan-2-yl)-2-methyl-1H-indole-3-carbaldehyde (510 mg, 57%) as a light yellow oil. LCMS (M+H+) m/z: calcd. 245.14. found 245.9.

Workup

  1. customThe resultant reaction mixture
  2. customThen the resulting reaction mixture
  3. stirringto stir for 1 hour at 0° C.
  4. temperaturewarmed to the ambient temperature
  5. stirringto stir for 24 hours at room temperature
  6. customThe reaction mixture was quenched with saturated sodium acetate
  7. additionby progressively adding 2N sodium hydroxide below 0° C.
  8. extractionextracted with dichloromethane (100 mL×3)
  9. dry with materialThe combined organic phase was dried by anhydrous sodium sulphate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated
  12. custompurified by column chromatograph on silica gel
  13. washeluted with (petrol ether/acetic ester 10:1→5:1→2:1)

Sources & evidence

ORD record
ord-ad7e73c8e6134b0aaa1ae71f589c5ec3
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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