Reacción #2146712

Ecuación de reacción

19

5-tert-Butoxycarbonylamino-5-{2-[4-(5-hydroxyl-1-pentyl)phenyl]ethyl}-2,2-dimethyl-1,3-dioxane

N,N-diisopropylethylamine

lithium iodide

sodium azide

Methanesulfonyl chloride

→

20

Rendimiento 67.0%

5-tert-Butoxycarbonylamino-5-{2-[4-(5-azido-1-pentyl)phenyl]ethyl}-2,2-dimethyl-1,3-dioxane

Rendimiento 67.0%

Disolventes

Water

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroat room temperature
2. 2
   Otroovernight
3. 3
   LavadoThe mixture was washed with saturated aqueous NaHCO3 solution (2×10 mL), water (2×10 mL), and brine (2×10 mL)
4. 4
   Secadodried (Na2SO4)
5. 5
   OtroAfter the solvent was removed
6. 6
   workup.DISSOLUTIONthe residue was dissolved in dry DMF (5 mL)
7. 7
   workup.STIRRINGThe reaction mixture was stirred at 80° C. for 18 h
8. 8
   Temperaturawas cooled to room temperature
9. 9
   Extracciónthe suspension was extracted with CH2Cl2 (3×20 mL)
10. 10
    LavadoThe combined organic layer was washed with water (3×30 mL) and brine (2×20 mL)
11. 11
    Secadodried (Na2SO4)
12. 12
    Concentraciónconcentrated under vacuum
13. 13
    OtroThe residue was purified by chromatography (hexanes/EtOAc 4:1)

Procedimiento

A solution of 19 (168 mg, 0.40 mmol) and N,N-diisopropylethylamine (155 mg, 1.2 mmol) in CH2Cl2 (10 mL) was cooled to 0° C. Methanesulfonyl chloride (66 mg, 0.60 mmol) was added, and the mixture was stirred at 0° C. for 2 h and then at room temperature overnight. The mixture was washed with saturated aqueous NaHCO3 solution (2×10 mL), water (2×10 mL), and brine (2×10 mL), and then dried (Na2SO4). After the solvent was removed, the residue was dissolved in dry DMF (5 mL) and lithium iodide (7 mg, 48 μmol) and sodium azide (78 mg, 1.2 mmol) were added. The reaction mixture was stirred at 80° C. for 18 h and then was cooled to room temperature. Water (15 mL) was added, and the suspension was extracted with CH2Cl2 (3×20 mL). The combined organic layer was washed with water (3×30 mL) and brine (2×20 mL), dried (Na2SO4), and concentrated under vacuum. The residue was purified by chromatography (hexanes/EtOAc 4:1) to give 20 (119 mg, 67%). 1H NMR δ 7.14-7.04 (m, 4H), 5.02 (s, 1H), 3.89 (d, 2H, J=11.6 Hz), 3.67 (d, 2H, J=11.6 Hz), 3.24 (t, 2H, J=7.2 Hz), 2.60-2.50 (m, 4H), 1.97 (t, 2H, J=8.0 Hz), 1.66-1.56 (m, 4H), 1.47 (s, 9H), 1.43 (s, 3H), 1.41 (s, 3H), 1.40-1.36 (m, 2H); 13C NMR δ 154.7, 139.7, 139.2, 128.3, 128.2, 98.2, 79.1, 66.2, 51.6, 51.2, 35.2, 33.5, 30.9, 28.6, 28.5, 28.3, 27.3, 26.2, 19.6. HRMS m/z: calcd for C24H38N4NaO4 (MNa+), 469.2785; found, 469.2786.

Fuente