반응 #87492

반응 방정식

acetic acid 2-bromo-ethyl ester

(1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-hydroxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol

potassium carbonate

Water

acetic acid 2-bromo-ethyl ester

→

Acetic acid 2-{4-[2-chloro-5-((1S,2S,3S,4R,5S)-2,3,4-trihydroxy-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]oct-5-yl)-benzyl]-phenoxy}-ethyl ester

수율 22.0%

용매

acetonitrile

ethyl acetate

반응 조건

후처리

1. 1
   온도the resulting mixture was heated to 50 degrees Celsius for 72 hours
2. 2
   온도the mixture was heated at 50 degrees Celsius for an additional 24 hours
3. 3
   기타the two phases separated
4. 4
   추출the aqueous phase was extracted 3 times with ethyl acetate (20 mL)
5. 5
   세척The combined organic layers were washed with brine
6. 6
   건조dried over sodium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated under reduced pressure
9. 9
   기타The crude material was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (4 g silica gel column)
10. 10
    세척eluting with a gradient of 0 to 30% methanol in dichloromethane
11. 11
    workup.ADDITION10 mg (22% yield) of a ˜2:1 mixture of the desired product
12. 12
    기타was obtained

실험 절차

To a solution of (1S,2S,3S,4R,5S)-5-[4-chloro-3-(4-hydroxy-benzyl)-phenyl]-1-hydroxymethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol (38 mg, 0.093 mmol) in acetonitrile (0.9 mL) was added potassium carbonate (40 mg, 0.28 mmol) followed by the addition of acetic acid 2-bromo-ethyl ester (0.012 mL, 0.112 mmol) and the resulting mixture was heated to 50 degrees Celsius for 72 hours. The reaction showed some product formation but the majority of starting material remained. An additional 2 equivalents of acetic acid 2-bromo-ethyl ester was added and the mixture was heated at 50 degrees Celsius for an additional 24 hours. Water (20 mL) and ethyl acetate were added, the two phases separated and the aqueous phase was extracted 3 times with ethyl acetate (20 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography over silica gel using the ISCO automated chromatography unit (4 g silica gel column) and eluting with a gradient of 0 to 30% methanol in dichloromethane. 10 mg (22% yield) of a ˜2:1 mixture of the desired product contaminated with some unidentified compound was obtained. LCMS 539 M+HCOO−, negative mode).

출처