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

HRID 720959

反応式

HRID 720959 の反応式
[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

参加物

5

反応物 3

HCID 962WaterHCID 12671Methyl phosphonic dichlorideHCID 97865N-Acetylcolchicinol

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒4 回

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-de37eb0acdf1431ebb324dd7a7236732
出典データセット
uspto-grants-2006_11
特許番号
US07135502B1

関連ノート

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