反応 #162590

反応方程式

NEt3

2,4-dichloropyrimidine

8-oxa-3-aza-bicyclo[3.2.1]octane hydrochloride

→

3-(2-chloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

収率 89.0%

3-(2-Chloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

収率 89.0%

3-(4-chloro-pyrimidin-2-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

収率 4.0%

溶媒

EtOH

反応条件

後処理

1. 1
   濃縮The mixture was concentrated
2. 2
   workup.DISSOLUTIONdissolved in EtOAc
3. 3
   洗浄washed with saturated NaHCO3
4. 4
   抽出The aqueous phase was extracted with EtOAc
5. 5
   乾燥the combined organic phases were dried (MgSO4)
6. 6
   ろ過filtered
7. 7
   濃縮concentrated
8. 8
   その他The mixture was purified by silica gel chromatography (20-70% EtOAc in hexanes)

実験手順

A 745 mg (5 mmol) portion 2,4-dichloropyrimidine (1) was dissolved in 20 mL EtOH at 0 C. 8-oxa-3-aza-bicyclo[3.2.1]octane hydrochloride (2, 748 mg, 5 mmol) was added followed by the addition of NEt3 (2.1 mL, 15 mmol). The mixture was stirred for 1 hour at ambient temperature. The mixture was concentrated, dissolved in EtOAc and washed with saturated NaHCO3. The aqueous phase was extracted with EtOAc and the combined organic phases were dried (MgSO4), filtered and concentrated. The mixture was purified by silica gel chromatography (20-70% EtOAc in hexanes) to give 1,003 mg (4.4 mmol, 89%) of 3-(2-chloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (3) along with 50 mg (0.22 mmol, 4%) of 3-(4-chloro-pyrimidin-2-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (4).

出典