Triethylamine → 2-(4-Methoxyphenyl)-1,1-dimethylethylamine

HRID 602051Notes

Reaction equation

HRID 602051 reaction equation
[CH3:1][C:2](C)([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)[C:3](O)=O.C([N:18](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1(C)C=CC=CC=1.O1CCOCC1.Cl.O.ClCCl>[CH3:1][C:2]([NH2:18])([CH3:3])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1

Participants

9

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 226408683-(4-Methoxyphenyl)-2,2-dimethylpropanoic acid

Product 1

HCID 918922-(4-Methoxyphenyl)-1,1-dimethylethylamineYield 65.6%

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,2-dimethyl-3-(4-methoxyphenyl)propanoic acid (36.0 g, 0.17 mol) in toluene (160 mL) was added triethylamine (19.2 g, 0.19 mol) and cooled to 0° C. To this cooled mixture was added diphenylphosphoryl azide (52.3 g, 0.19 mol) and the reaction mixture was stirred at room temperature for 15 min and then heated at 75° C. for 2.5 h. The progress of the reaction was monitored by TLC. After the completion of the reaction, as indicated by TLC it was cooled to room temperature and quenched with water (500 mL) and extracted with EtOAc (2×500 mL). The organic extracts were combined and dried over Na2SO4, filtered and concentrated to give an oil. This oil was dissolved in a mixture of 1,4-dioxane (108 mL) and 6 N HCl (180 mL) and heated at reflux for 1 h. After 1 h, the reaction mixture was cooled to room temperature and diluted with water (100 mL) and dichloromethane (400 mL). The organic layer was separated and pH of the aqueous layer was adjusted to ˜14 with 6 M NaOH (200 mL) and extracted with dichloromethane (3×500 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give 20.0 g (65%) of 2-methyl-1-(4-methoxyphenyl)-2-propanamine as a yellow oil; 1H NMR (200 MHz, CDCl3) δ 7.10 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 3.79 (s, 3H), 2.59 (s, 2H), 1.10 (s, 6H).

Workup

  1. temperatureheated at 75° C. for 2.5 h
  2. customAfter the completion of the reaction
  3. temperaturewas cooled to room temperature
  4. customquenched with water (500 mL)
  5. extractionextracted with EtOAc (2×500 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give an oil
  10. temperatureheated
  11. temperatureat reflux for 1 h
  12. waitAfter 1 h
  13. temperaturethe reaction mixture was cooled to room temperature
  14. customThe organic layer was separated
  15. extractionextracted with dichloromethane (3×500 mL)
  16. dry with materialThe combined organic extracts were dried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated

Sources & evidence

ORD record
ord-0217e4b93ac5443fa4da37c63a2c9ffc
Source dataset
uspto-grants-2011_03
Patent number
US07902394B2

Reaction notes

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