Hydrochloric Acid → HCID 57461073, compound

HRID 2113266Notes

Reaction equation

HRID 2113266 reaction equation
[CH2:1]([N:8]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:9]1[CH:14]=[C:13]([CH3:15])[C:12](I)=[CH:11][C:10]=1[CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:32]=[O:33].[ClH:35]>C1(C)C=CC=CC=1>[ClH:35].[CH2:1]([N:8]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:9]1[C:10]([CH3:17])=[CH:11][C:12]([CH:32]=[O:33])=[C:13]([CH3:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 57461072Dibenzyl-(4-iodo-2,5-dimethylphenyl)amineHCID 178418339Butyllithium

Product 1

HCID 57461073HCID 57461073, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-20 °C

Procedure

To a 1-liter 3-necked round-bottomed flask equipped with an overhead stirrer, temperature control and an addition funnel was added dibenzyl-(4-iodo-2,5-dimethylphenyl)amine (15 g, 35 mmol). Toluene (300 mL) was added and the resulting mixture was stirred for about 15 minutes. The reaction flask was purged with dry nitrogen and cooled to about −20° C. and 1.6 M n-butyllithium in hexanes (33 mL, 53 mmol) was added dropwise via the addition funnel. During the addition, the internal temperature of the reaction mixture was maintained below −10° C. When the addition was complete, the resulting mixture was stirred at about −15° C. for 15 minutes. N,N-Dimethylformamide (10 mL, 129 mmol) was then added dropwise while maintaining the internal reaction temperature below 0° C. The resulting mixture was then stirred at −20° C. to 0° C. for about 1 hour. Aqueous 1 M hydrochloric acid (200 mL) was then added over a 5 minute period and the resulting mixture was stirred for 15 minutes. The layers were then separated and the organic layer was washed with dilute brine (100 mL). The organic layer was then dried over anhydrous sodium sulfate, filtered and the solvent removed under reduced pressure to provide 4-dibenzylamino-2,5-dimethylbenzaldehyde hydrochloride (11.5 g, 90% yield, 95% purity) as thick oil that solidified upon standing. The product contained about 3 to 5% of the des-iodo by-product. 1H NMR (300 MHz, CDCl3) δ 2.42 (s, 3H), 2.50 (s, 3H), 4.25 (s, 4H), 6.82 (s, 1H), 7.10-7.30 (m, 10H), 7.62 (s, 1H), 10.15 (s, 1H); MS [M+H+] found 330.3.

Workup

  1. customTo a 1-liter 3-necked round-bottomed flask equipped with an overhead stirrer
  2. customThe reaction flask was purged with dry nitrogen
  3. additionDuring the addition
  4. temperaturethe internal temperature of the reaction mixture was maintained below −10° C
  5. additionWhen the addition
  6. stirringthe resulting mixture was stirred at about −15° C. for 15 minutes
  7. temperaturewhile maintaining the internal reaction temperature below 0° C
  8. stirringThe resulting mixture was then stirred at −20° C. to 0° C. for about 1 hour
  9. stirringthe resulting mixture was stirred for 15 minutes
  10. customThe layers were then separated
  11. washthe organic layer was washed with dilute brine (100 mL)
  12. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-5c7df20454a6446a9afdb7121d99891b
Source dataset
uspto-grants-2009_04
Patent number
US07524965B2

Reaction notes

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