반응 #48763

반응 방정식

sodium sulfite

N-iodosuccinimide

vinblastine hydrogensulfate

sodium hydrogencarbonate

→

12′-iodovinblastine

수율 112.4%

용매

trifluoroacetic acid methylene chloride

trifluoroacetic acid methylene chloride

반응 조건

후처리

1. 1
   workup.ADDITIONaddition funnel
2. 2
   workup.ADDITIONAfter the addition
3. 3
   workup.ADDITIONthen poured carefully into
4. 4
   workup.STIRRINGa rapidly stirring
5. 5
   추출The solution was then extracted with chloroform (3×50 mL)
6. 6
   세척the combined organic extracts were washed with 10% sodium sulfite (50 mL) and brine (50 mL)
7. 7
   건조dried over magnesium sulfate
8. 8
   기타The solvent was remove in vacuo

실험 절차

A solution of N-iodosuccinimide (254 mg, 1.13 mmol) in trifluoroacetic acid/methylene chloride (1:1, 16 mL) was cooled to approximately 0° C. in an ice-water jacketed addition funnel then added dropwise to vinblastine hydrogensulfate (1.08 g, 1.19 mmol) in trifluoroacetic acid/methylene chloride (1:1, 32 mL) at −15° C. The temperature was monitored by an internal thermometer and maintained at −15±3° C. during the course of the addition (45 min). After the addition was complete, the reaction mixture was stirred 10 min then poured carefully into a rapidly stirring mixture of 10% sodium sulfite/satd sodium hydrogencarbonate/chloroform (1:2:2, 200 mL). Solid sodium hydrogencarbonate was then added in small portions until gas evolution stopped. The solution was then extracted with chloroform (3×50 mL) and the combined organic extracts were washed with 10% sodium sulfite (50 mL) and brine (50 mL) and dried over magnesium sulfate. The solvent was remove in vacuo to provide 12′-iodovinblastine (1.19 g, quantitative) as a tan foam which was carried forward without further purification: 1H NMR (500 MHz, CD3OD) δ 7.75 (d, J=1.1 Hz, 1H), 7.32 (dd, J=8.4, 1.4 Hz, 1H), 7.00 (d, J=8.5 Hz, 1H), 6.56 (s, 1H), 6.31 (s, 1H), 5.83 (dd, J=10.2, 3.9 Hz, 1H), 5.36 (s, 1H), 5.29 (d, J=10.2 Hz, 1H), 3.91-4.07 (m, 2H), 3.81 (s, 3H), 3.76 (s, 3H), 3.64 (s, 3H), 3.58 (s, 1H), 3.36 (d, J=14.3 Hz, 1H), 3.30 (m, 1H), 3.15-3.27 (m, 3H), 2.94 (dd, J=14.8, 4.0 Hz, 1H), 2.71-2.85 (m, 4H), 2.71 (s, 3H), 2.41-2.49 (m, 2H), 2.26 (dd, J=15.6-3.6 Hz, 1H), 2.07 (m, 1H), 2.02 (s, 3H), 1.87 (m, 1H), 1.66 (m, 1H), 1.50 (d, J=14.1 Hz, 1H), 1.41 (m, 2H), 1.32 (q, J=7.4 Hz, 2H), 0.90 (t, J=7.5 Hz, 3H), 0.81 (m, 1H), 0.75 (t, J=7.3 Hz, 3H); ESI MS m/z 937 [M+H]+.

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