Dimethylformamide → HCID 21070813, compound

HRID 1371345Notes

Reaction equation

HRID 1371345 reaction equation
CN([CH:4]=[O:5])C.P(Cl)(Cl)(Cl)=O.[CH2:11]([C:13]1[C:14]([NH:20][CH2:21][CH2:22][NH:23][C:24](=[O:26])[CH3:25])=[C:15]([OH:19])[CH:16]=[CH:17][CH:18]=1)[CH3:12].[OH-].[Na+]>O>[OH:19][C:15]1[C:14]([NH:20][CH2:21][CH2:22][NH:23][C:24](=[O:26])[CH3:25])=[C:13]([CH2:11][CH3:12])[CH:18]=[CH:17][C:16]=1[CH:4]=[O:5]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 14798Sodium Hydroxide2×HCID 24813Phosphorus oxychloride2×HCID 21070815HCID 21070815, compound

Product 1

HCID 21070813HCID 21070813, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

A scrupulously dry flask was charged with anhydrous DMF (15 ml) and cooled in ice under argon. Phosphorus oxychloride, POCl3, 1.5 ml (1.15 eq) was added slowly dropwise to the stirred solution. After the addition was complete, the flask was removed from the ice bath and allowed to reach ambient temperature. This was accompanied by a color change to yellow. The flask was heated in a 40° C. bath for one hour. It was removed from the heat, and once at ambient temperature, a DMF solution of 3-(ethyl)(2-acetylaminoethyl)aminophenol (8; 3.2 g, 14 mmol) was added via addition funnel. After the addition was complete, the flask was returned to the 40° C. bath and stirred overnight. The reaction was cooled to 0° C. and 25 ml 10% NaOH was added, the mixture was allowed to warm to ambient temperature and was then placed in a 40° C. bath. Additional NaOH was added to achieve pH>10. Water (50 ml) was added. After 15 minutes the flask was removed from the bath and the pH adjusted to 5–5.5 with 1N HCl. The mixture was transferred to a separatory funnel and extracted with 4×100 ml ethyl acetate. The pooled organic fractions were washed with water (1×75 ml), predried with Na2SO4, and then dried with MgSO4 overnight. The solution was collected by filtration and the volatiles removed by rotary evaporation to yield the crude product (2.9 g). The material was purified by flash chromatography on silica, 45×150 mm column, eluting with 200 ml each of 2.5%, 5%, and 10% methanol/chloroform. Purified yield of (2-hydroxy-4-(ethyl)(2-acetylaminoethyl)aminobenzaldehyde) (9) was 1.52 g (45%).

Workup

  1. temperaturecooled in ice under argon
  2. additionAfter the addition
  3. customthe flask was removed from the ice bath
  4. customto reach ambient temperature
  5. customIt was removed from the heat
  6. additionAfter the addition
  7. customwas returned to the 40° C. bath
  8. temperatureThe reaction was cooled to 0° C.
  9. temperatureto warm to ambient temperature
  10. customwas then placed in a 40° C.
  11. customAfter 15 minutes the flask was removed from the bath
  12. customThe mixture was transferred to a separatory funnel
  13. extractionextracted with 4×100 ml ethyl acetate
  14. washThe pooled organic fractions were washed with water (1×75 ml)
  15. dry with materialdried with MgSO4 overnight
  16. filtrationThe solution was collected by filtration
  17. customthe volatiles removed by rotary evaporation

Sources & evidence

ORD record
ord-c20527ba6cfe4b9cbd35f907ea84a04b
Source dataset
uspto-grants-2007_01
Patent number
US07157458B2

Reaction notes

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