Water → (5s)-5-(Acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5h-dibenzo[a,c]cyclohepten-3-yl hydrogen methylphosphonate

HRID 720959

반응식

HRID 720959 반응식
[CH3:1][C:2]([NH:4][CH:5]1[C:15]2[CH:16]=[C:17]([OH:20])[CH:18]=[CH:19][C:14]=2[C:13]2[C:8](=[CH:9][C:10]([O:25][CH3:26])=[C:11]([O:23][CH3:24])[C:12]=2[O:21][CH3:22])[CH2:7][CH2:6]1)=[O:3].[CH3:27][P:28](Cl)(Cl)=[O:29].[OH2:32]>C1COCC1>[CH3:27][P:28](=[O:29])([OH:32])[O:20][C:17]1[CH:18]=[CH:19][C:14]2[C:13]3[C:12]([O:21][CH3:22])=[C:11]([O:23][CH3:24])[C:10]([O:25][CH3:26])=[CH:9][C:8]=3[CH2:7][CH2:6][C@H:5]([NH:4][C:2](=[O:3])[CH3:1])[C:15]=2[CH:16]=1

참가 물질

5

반응물 3

HCID 962WaterHCID 12671Methyl phosphonic dichlorideHCID 97865N-Acetylcolchicinol

생성물 1

HCID 57252105(5s)-5-(Acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5h-dibenzo[a,c]cyclohepten-3-yl hydrogen methylphosphonate수율 41%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매4회

반응 조건

온도
0 °C

실험 절차

A solution of N-acetyl-colchicinol (0.36 g; 1.0 mmol) in THF (40 ml) under argon was cooled to 0° C. and treated with a 1.0M solution of lithiumHMDS in THF (1.1 ml; 1.1 mmol). The mixture was stirred at 0° C. for 1 hour and then added in portions over about 2 hours to a solution of methylphosphonic dichloride (0.53 mg; 4.0 mmol) in THF (150 ml). The mixture was stirred at ambient temperature for 15 minutes. After addition of water (200 ml) the THF was removed by evaporation. After removal of the insoluble material by filtration, the filtrate was purified on HP20 SS resin eluting with a gradient of 0–60% methanol/water. The methanol was removed by evaporation and the mixture was adjusted to pH7.14 with sodium hydroxide (0.1 M). The appropriate fractions were freeze-dried to give (5S)-5-(acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl hydrogen methylphosphonate as a beige solid (180 mg).

후처리

  1. stirringThe mixture was stirred at ambient temperature for 15 minutes
  2. customwas removed by evaporation
  3. customAfter removal of the insoluble material
  4. filtrationby filtration
  5. customthe filtrate was purified on HP20 SS resin
  6. washeluting with a gradient of 0–60% methanol/water
  7. customThe methanol was removed by evaporation
  8. customThe appropriate fractions were freeze-dried

출처 및 근거

ORD 기록
ord-de37eb0acdf1431ebb324dd7a7236732
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07135502B1

연결된 노트

불러오는 중…