Toluene → N-(1-benzyl-7-bromo-3,4-dihydronaphthalen-2-yl)propionamide

HRID 587796Notes

Reaction equation

HRID 587796 reaction equation
[CH2:1]([CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([Br:18])[CH:16]=2)[CH2:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([NH2:24])(=[O:23])[CH2:21][CH3:22].CC1C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>CC(O)C>[CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([Br:18])[CH:16]=2)[CH2:11][CH2:10][C:9]=1[NH:24][C:20](=[O:23])[CH2:21][CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 6578PropionamideHCID 729463081-benzyl-7-bromo-3,4-dihydronaphthalen-2(1H)-one

Product 1

HCID 86707883N-(1-benzyl-7-bromo-3,4-dihydronaphthalen-2-yl)propionamideYield 81.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

In a three-necked flask equipped with a Dean-Stark apparatus, heating mantle and magnetic stirrer were charged 1-benzyl-7-bromo-3,4-dihydronaphthalen-2(1H)-one (23.50 g, 74.6 mmol), propionamide (13.62 g, 186 mmol) and 4-methylbenzenesulfonic acid (1.284 g, 7.46 mmol) followed by toluene (200 ml). The resulting solution was heated to reflux overnight and monitored by HPLC (<6% starting material remained). The reaction mixture was cooled to r.t. and a suspension formed. To the mixture was added IPA and the resulting suspension was cooled to 0° C., stirred at 0° C. for 2 hours and filtered. The filtrate was concentrated and the residue was suspended in IPA/EtOH (50 ml/50 ml) at 0° C. for 1 hr and filtered to give additional product as a white solid. HPLC analysis indicated that both crops have similar purity. The solids were combined and further dried to give 22.5 g product as white solid.

Workup

  1. customIn a three-necked flask equipped with a Dean-Stark apparatus
  2. temperatureheating mantle
  3. temperatureThe resulting solution was heated
  4. temperatureto reflux overnight
  5. customa suspension formed
  6. temperaturethe resulting suspension was cooled to 0° C.
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. waitthe residue was suspended in IPA/EtOH (50 ml/50 ml) at 0° C. for 1 hr
  10. filtrationfiltered
  11. customto give additional product as a white solid
  12. customfurther dried

Sources & evidence

ORD record
ord-d7c24fafd6854287889d9eb5c4ae0289
Source dataset
uspto-grants-2016_01
Patent number
US09227901B2

Reaction notes

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