Tetrahydrofuran → HCID 5358230、化合物

HRID 2218492ノート

反応式

HRID 2218492 の反応式
[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([O:30]C(CC(C)C)=O)[CH2:24][C:22](=[O:23])[N:21]([CH3:37])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:38])=[CH:9][CH:8]=[CH:7][CH:6]([O:39][CH3:40])[C:5]2([OH:45])[NH:41][C:42]([O:44][CH:3]1[CH2:4]2)=[O:43].O1CCCC1>O>[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([OH:30])[CH2:24][C:22](=[O:23])[N:21]([CH3:37])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:38])=[CH:9][CH:8]=[CH:7][CH:6]([O:39][CH3:40])[C:5]2([OH:45])[NH:41][C:42]([O:44][CH:3]1[CH2:4]2)=[O:43]

参加物

4

反応物 2

HCID 8028Tetrahydrofuran2 回HCID 99958HCID 99958、化合物

生成物 1

HCID 5358230HCID 5358230、化合物収率 85%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
-50 °C

実験手順

Ansamitocins (3.0 g, 4.72 mmol) were weighed into a three necked flask equipped with a thermometer. Tetrahydrofuran (15 mL) was added to the flask with stirring and the flask was cooled in a −50° C. cooling bath. Once the contents of the flask reached −35° C., a solution of 0.67 M LiAl(OMe)3H in tetrahydrofuran (56 mL, 37.7 mmol) was added dropwise by syringe using a syringe pump. The temperature of the reaction was maintained between −30° C. and −40° C. throughout the addition. After addition was complete, the reaction was stirred for 2 hours at between −32° C. and −37° C. Deionized water (7.7 mL) was added dropwise to the −35° C. reaction to give a basic quenched mixture. The basic quenched mixture was analyzed after set holding periods by the thin layer chromatography assay described in Example 6. The compound of Formula (I) was detected after holding for 5 and 15 minutes. After 30 min a sample of the basic quenched mixture was analyzed again by the thin layer chromatography method. The compound of Formula (I) was no longer detected. Aqueous formic acid (deionized water, 15 mL and 88% formic acid, 1.85 mL) was then added to the flask followed by 66 mL of ethyl acetate. The cooling unit was turned off, and the mixture was allowed to slowly warm to room temperature. The pH of the mixture was checked with pH paper and found to be approximately pH 6. The precipitated aluminum byproducts were removed by vacuum filtration. Solvent was evaporated from the filtrate by rotary evaporation under vacuum. Butyl acetate was added to the residue, the solvent was then evaporated to remove any remaining water The residue was purified by silica chromatography using a mobile phase of dichloromethane:methanol 95:5 (v:v) to give 2.2 g of maytansinol (85% yield by weight).

後処理

  1. customequipped with a thermometer
  2. temperaturecooling bath
  3. customreached −35° C.
  4. temperatureThe temperature of the reaction was maintained between −30° C. and −40° C. throughout the addition
  5. additionAfter addition
  6. stirringthe reaction was stirred for 2 hours at between −32° C. and −37° C
  7. customto give a basic
  8. customquenched mixture
  9. customThe basic quenched mixture
  10. customafter holding for 5 and 15 minutes
  11. customAfter 30 min a sample of the basic quenched mixture
  12. additionAqueous formic acid (deionized water, 15 mL and 88% formic acid, 1.85 mL) was then added to the flask
  13. temperatureto slowly warm to room temperature
  14. customThe precipitated aluminum byproducts were removed by vacuum filtration
  15. customSolvent was evaporated from the filtrate by rotary evaporation under vacuum
  16. additionButyl acetate was added to the residue
  17. customthe solvent was then evaporated
  18. customto remove any remaining water The residue
  19. customwas purified by silica chromatography

出典と根拠

ORDレコード
ord-5041f19b4b8245da994d1c3c11f13b13
出典データセット
uspto-grants-2008_08
特許番号
US07411063B2

反応ノート

読み込み中…