2-Isopropylphenol → JW 480

HRID 1771943Notes

Reaction equation

HRID 1771943 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10])([CH3:3])[CH3:2].ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.CCN(CC)CC.[C:31]([O-:34])(O)=O.[Na+].C(=O)([O-])[O-].[CH:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[CH:42][C:41]=1[CH2:50][CH2:51][NH2:52]>ClCCl.C(OCC)(=O)C>[CH:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[CH:43]=[CH:42][C:41]=1[CH2:50][CH2:51][NH:52][C:31](=[O:34])[O:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[CH:1]([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 69432-IsopropylphenolHCID 8471Triethylamine2×HCID 19660Carbonate IonHCID 821294-Nitrophenyl chloroformateHCID 516892Sodium Bicarbonate2×HCID 37843782-(2-Naphthyl)ethyl-amine

Product 1

HCID 57330099JW 480Yield 94%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-isopropylphenol (5.0 g, 36.713 mmol) in dichloromethane (183.0 mL) was added 4-nitrophenyl chloroformate (8.1 g, 40.385 mmol) and Et3N (10.3 mL, 73.426 mmol) at 0° C. After stirring at 0° C. 2 hours, the reaction mixture was treated with 30.0 mL of saturated aqueous NaHCO3 solution. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was used without further purification. To a solution of crude carbonate intermediate in dichloromethane (150 mL) was added 2-(naphthalen-2-yl)ethanamine (6.9 g, 40.385 mmol) and Et3N (10.3 mL, 73.426 mmol) at 0° C. After stirring at 0° C. 2 hours, the reaction mixture was treated with 30.0 mL of saturated aqueous NaHCO3 solution. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by flash column chromatography using a 9:1 v/v hexane:ethyl acetate as solvent to afford title compound (11.5 g, 94% yield) as a white solid.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with dichloromethane
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was used without further purification
  8. stirringAfter stirring at 0° C
  9. customThe organic layer was separated
  10. extractionthe aqueous layer was extracted with dichloromethane
  11. washThe combined organic extracts were washed with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-b798813aa4ef42dc961fc9c264b57371
Source dataset
uspto-grants-2016_02
Patent number
US09249128B2

Reaction notes

Loading…