反応 #2146712

反応方程式

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

収率 67.0%

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

収率 67.0%

溶媒

Water

CH2Cl2

反応条件

後処理

1. 1
   その他at room temperature
2. 2
   その他overnight
3. 3
   洗浄The mixture was washed with saturated aqueous NaHCO3 solution (2×10 mL), water (2×10 mL), and brine (2×10 mL)
4. 4
   乾燥dried (Na2SO4)
5. 5
   その他After 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
   温度was cooled to room temperature
9. 9
   抽出the suspension was extracted with CH2Cl2 (3×20 mL)
10. 10
    洗浄The combined organic layer was washed with water (3×30 mL) and brine (2×20 mL)
11. 11
    乾燥dried (Na2SO4)
12. 12
    濃縮concentrated under vacuum
13. 13
    その他The residue was purified by chromatography (hexanes/EtOAc 4:1)

実験手順

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.

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