Triethylamine → HCID 10263798, compound

HRID 1042467Notes

Reaction equation

HRID 1042467 reaction equation
[NH2:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].C(N(CC)CC)C.[F:14][C:15]([F:25])([F:24])[C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Cl)=[CH:18][CH:17]=1>C1COCC1>[CH3:5][C:2]1([CH3:6])[CH2:3][O:4][C:20]([C:19]2[CH:18]=[CH:17][C:16]([C:15]([F:14])([F:24])[F:25])=[CH:23][CH:22]=2)=[N:1]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 118072-Amino-2-methyl-1-propanolHCID 123096p-Trifluoromethylbenzyl chloride

Product 1

HCID 10263798HCID 10263798, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cold solution of 2-amino-2-methyl-1-propanol (21.4 g, 240 mmol) and triethylamine (16.8 mL, 120 mmol) in THF was added dropwise 4-trifluoromethyl benzyl chloride (25.0 g, 120 mmol). After the addition, the reaction mixture was stirred at 0° C. for 30 mins and then stirred at ambient temperature for 8 hrs. The precipitate was removed by filtration and the filtrate was concentrated by evaporating the solvent under reduced pressure. The resulting residue was treated dropwise with thionyl chloride with vigorous stirring at 0° C. After complete addition, the reaction mixture was further stirred at ambient temperature for 1 hr. Ether was poured into the reaction mixture and the precipitate was collected by filtration. The precipitate was dissolved in water and the aqueous solution was hydrolyzed with 10% (w/v) NaOH. The aqueous phase was extracted three times with ether, and the combined organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The crude residue was purified by column chromatography (Hex/EtOAc=5/1) to yield the title compound (25.4 g, 87%).

Workup

  1. additionAfter the addition
  2. stirringstirred at ambient temperature for 8 hrs
  3. customThe precipitate was removed by filtration
  4. concentrationthe filtrate was concentrated
  5. customby evaporating the solvent under reduced pressure
  6. additionThe resulting residue was treated dropwise with thionyl chloride
  7. stirringwith vigorous stirring at 0° C
  8. additionAfter complete addition
  9. stirringthe reaction mixture was further stirred at ambient temperature for 1 hr
  10. additionEther was poured into the reaction mixture
  11. filtrationthe precipitate was collected by filtration
  12. dissolutionThe precipitate was dissolved in water
  13. extractionThe aqueous phase was extracted three times with ether
  14. washthe combined organic layer was washed with brine
  15. dry with materialdried over anhydrous MgSO4
  16. concentrationconcentrated under reduced pressure
  17. customThe crude residue was purified by column chromatography (Hex/EtOAc=5/1)

Sources & evidence

ORD record
ord-e48cebb0851d489b89812967e790c158
Source dataset
uspto-grants-2013_10
Patent number
US08557872B2

Reaction notes

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