반응 #87473

반응 방정식

potassium carbonate

(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

(2-bromo-ethoxymethyl)-benzene

→

desired compound

수율 26.0%

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

수율 26.0%

용매

acetonitrile

ethyl acetate

반응 조건

후처리

1. 1
   온도the reaction mixture was heated to 50 degrees Celsius for 24 hours
2. 2
   온도the temperature was increased to 83 degrees Celsius
3. 3
   기타the organic phase 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 23% methanol in dichloromethane

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 (14 mg, 0.034 mmol) in acetonitrile (0.5 mL) was added potassium carbonate (14 mg, 0.1 mmol) followed by the addition of (2-bromo-ethoxymethyl)-benzene (0.010 mL, 0.063 mmol) and the reaction mixture was heated to 50 degrees Celsius for 24 hours. The reaction showed some product formation but the majority of starting material remained. An additional 3 equivalents of potassium carbonate was added, the temperature was increased to 83 degrees Celsius and the reaction mixture stirred for an additional 5 hours. The reaction mixture was cooled to room temperature, water (20 mL) and ethyl acetate were added, the organic phase 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 23% methanol in dichloromethane. 4 mg of the desired compound (1S,2S,3S,4R,5S)-5-(3-(4-(2-(Benzyloxy)ethoxy)benzyl)-4-chlorophenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol was obtained. LCMS 587 (M+HCO2−, negative mode). 1H NMR (500 MHz, METHANOL-d4) delta ppm 3.56 (d, J=8.1 Hz, 1 H), 3.60 (d, J=7.6 Hz, 1 H), 3.63-3.67 (m, 1 H), 3.69 (d, J=12.7 Hz, 2 H), 3.79 (d, J=8.3 Hz, 1 H), 3.82 (d, J=4.6 Hz, 1 H), 3.83-3.87 (m, 1 H), 4.05 (s, 2 H), 4.11-4.14 (m, 2 H), 4.16 (d, J=7.3 Hz, 1 H), 4.62 (s, 2 H), 6.86 (d, J=8.5 Hz, 2 H), 7.12 (d, J=8.5 Hz, 2 H), 7.29 (d, J=7.1 Hz, 1 H), 7.31-7.43 (m, 6 H), 7.47 (s, 1 H).

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