Triethylamine → HCID 10268651, compound

HRID 1072652Notes

Reaction equation

HRID 1072652 reaction equation
[Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][C@@H:7]([CH3:10])[CH2:8][NH2:9])=[CH:4][CH:3]=1.[OH-].[Na+].C(N(CC)CC)C.[CH:22]([S:25](Cl)(=[O:27])=[O:26])([CH3:24])[CH3:23]>C(Cl)Cl.C(OC(=O)C)C.CCCCCC>[Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][C@@H:7]([CH3:10])[CH2:8][NH:9][S:25]([CH:22]([CH3:24])[CH3:23])(=[O:27])=[O:26])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 824082-Propanesulfonyl chlorideHCID 20806721(2S)-2-(4-Bromophenoxy)-1-propanamine

Product 1

HCID 10268651HCID 10268651, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
-20 °C

Procedure

To a reaction mixture of (2S)-2-(4-bromophenoxy)propylamine (19.0 g, 71.275 mmoles) and methylene chloride (200.0 ml) at room temperature was added 2N NaOH (150.0 ml) all at once with vigorous stirring for 45 minutes. The organic layer was separated, dried anhydrous magnesium sulfate, filtered, and the filtrate concentrated to an oil (16.22 g). To a solution of this oil in methylene chloride (225.0 ml) at room temperature was then added triethylamine (23.6 ml, 169.23 mmol) and N,N-dimethylaminopyridine (0.43 g) with stirring. The solution was cooled to −20° C. with dry ice/acetone bath, and a solution of isopropylsulfonyl chloride (9.5 ml, 84.62 mmol) dissolved in methylene chloride (25 ml) was added over a period of 30 minutes while maintaining the temperature at −20° C. The reaction was then stirred to room temperature overnight. The reaction was monitored with TLC (1:1 ethylacetate/hexane) until the reaction was complete. The reaction was quenched with 3N HCl solution (100.0 ml), the organic layer separated then dried with anhydrous magnesium sulfate. Subsequent filtration and concentration at reduced pressure afforded the final title compound (23.7 g, 100%) as an oil; 1H nmr (CDCl3) δ 1.25-1.26 (d, 3H, J=6.35 Hz), 1.33-1.35 (d, 6H, J=6.83 Hz), 3.14-3.19 (m, 1H), 3.22-3.26 (m, 1H), 3.34-3.36 (m, 1H), 4.43-4.46 (m, 1H), 4.74-4.76 (m, NH), 6.77-6.79 (d, 2H, J=9.03 Hz), 7.35-7.37 (d, 2H, J=9.03 Hz); 13C nmr (CDCl3) δ 16.91, 48.59, 53.94, 74.13, 113.84, 118.09, 132.72, 156.51).

Workup

  1. customThe organic layer was separated
  2. filtrationdried anhydrous magnesium sulfate, filtered
  3. concentrationthe filtrate concentrated to an oil (16.22 g)
  4. customat room temperature
  5. additionwas added over a period of 30 minutes
  6. temperaturewhile maintaining the temperature at −20° C
  7. stirringThe reaction was then stirred to room temperature overnight
  8. customThe reaction was quenched with 3N HCl solution (100.0 ml)
  9. customthe organic layer separated
  10. dry with materialthen dried with anhydrous magnesium sulfate
  11. filtrationSubsequent filtration and concentration at reduced pressure

Sources & evidence

ORD record
ord-ae80163d86004cd4b42138e22e6bbd1d
Source dataset
uspto-grants-2005_06
Patent number
US06911476B2

Reaction notes

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