Реакция #71656

Уравнение реакции

HCl

1,4-dioxane

1,1-dimethylethyl (2R)-2-methyl-1-piperazinecarboxylate

DIPEA

4-[(trifluoromethyl)oxy]benzenesulfonyl chloride

→

title compound

Выход 90.1%

(3R)-3-methyl-1-({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)piperazine

Выход 90.1%

Растворители

DCM

Условия реакции

Обработка

1. 1
   КонцентрированиеThe reaction mixture was then concentrated under vacuum
2. 2
   workup.DISSOLUTIONre-dissolved in 1,4-dioxane (100 ml)
3. 3
   КонцентрированиеThe reaction mixture was concentrated under vacuum
4. 4
   workup.DISSOLUTIONre-dissolved in DCM (200 ml)
5. 5
   Промывкаwashed with 2M aqueous NaOH (2×50 ml)
6. 6
   СушкаThe organic layer was dried (MgSO4)
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated under vacuum
9. 9
   workup.DISSOLUTIONThe residue was dissolved in ether
10. 10
    Концентрированиеconcentrated under vacuum
11. 11
    workup.DISSOLUTIONThe oil was dissolved in MeOH (150 ml)
12. 12
    Промывкаwas washed with MeOH, DCM and MeOH again
13. 13
    ПромывкаThe product was eluted from the column with 2M ammonia in methanol, DCM
14. 14
    Концентрированиеconcentration under vacuum

Методика

To a solution of 1,1-dimethylethyl (2R)-2-methyl-1-piperazinecarboxylate (2.00 g, 9.99 mmol) in DCM (200 ml) was added DIPEA (3.66 ml, 20.97 mmol) and then 4-[(trifluoromethyl)oxy]benzenesulfonyl chloride (1.69 ml, 9.99 mmol) and the resulting mixture stirred at room temperature for 90 min. The reaction mixture was then concentrated under vacuum and re-dissolved in 1,4-dioxane (100 ml). A 4M solution of HCl in 1,4-dioxane (100 ml, 400 mmol) and a few drops of distilled water were added and the mixture stirred for 3 h. The reaction mixture was concentrated under vacuum, re-dissolved in DCM (200 ml) and washed with 2M aqueous NaOH (2×50 ml). The organic layer was dried (MgSO4), filtered and concentrated under vacuum. The residue was dissolved in ether and concentrated under vacuum. The oil was dissolved in MeOH (150 ml), applied to an SCX cartridge (50 g), which was washed with MeOH, DCM and MeOH again. The product was eluted from the column with 2M ammonia in methanol, DCM and then 2M ammonia in methanol; concentration under vacuum gave the title compound as a yellow transparent oil (2.92 g).

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