Trimethylaluminum → (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one

HRID 2191528ノート

反応式

HRID 2191528 の反応式
C([O:3][C:4]([C:6]1[C:7]([CH3:32])=[C:8](C(OC(C)(C)C)=O)[NH:9][C:10]=1[CH2:11][CH2:12][CH2:13][NH:14][CH2:15][C@H:16]([OH:24])[CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=O)C.C[Al](C)C>C1(C)C=CC=CC=1>[OH:24][C@@H:16]([CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[CH2:15][N:14]1[CH2:13][CH2:12][CH2:11][C:10]2[NH:9][CH:8]=[C:7]([CH3:32])[C:6]=2[C:4]1=[O:3]

参加物

4

反応物 2

HCID 16682925TrimethylaluminumHCID 59250085(S)-5-[3-(2-hydroxy-3-morpholin-4-yl-propylamino)-propyl]-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester

生成物 1

HCID 59250058(S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one収率 76.2%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

(S)-5-[3-(2-Hydroxy-3-morpholin-4-yl-propylamino)-propyl]-3-methyl-1H-pyrrole-2 and 4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 78d (580 mg, 1.28 mmol) were dissolved in 6 ml of toluene under an argon atmosphere, the reaction mixture was cooled in an ice-water bath, meanwhile a solution of trimethylaluminum in toluene (1.9 ml, 2 mol/L, 3.84 mmol) was added to the solution. Upon the completion of the addition, the ice-water bath was removed, and the reaction solution was heated to reflux for 24 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction was stopped. The reaction solution was concentrated under reduced pressure to remove the reaction solvent, added with 20 ml hydrochloric acid (6 mol/L) and stirred for 20 minutes, adjusted to about pH 12 with sodium hydroxide solution (12 mol/L) in an ice-water bath. The resulting mixture was extracted with dichloromethane (50 ml×2), the combined organic phase was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 78e (300 mg, yield 57.6%) as a white solid.

後処理

  1. temperaturethe reaction mixture was cooled in an ice-water bath
  2. additionUpon the completion of the addition
  3. customthe ice-water bath was removed
  4. temperaturethe reaction solution was heated
  5. temperatureto reflux for 24 hours
  6. concentrationThe reaction solution was concentrated under reduced pressure
  7. customto remove the reaction solvent
  8. additionadded with 20 ml hydrochloric acid (6 mol/L)
  9. customadjusted to about pH 12 with sodium hydroxide solution (12 mol/L) in an ice-water bath
  10. extractionThe resulting mixture was extracted with dichloromethane (50 ml×2)
  11. concentrationthe combined organic phase was concentrated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-8376ad9e69874faa89d547798cef56f3
出典データセット
uspto-grants-2012_12
特許番号
US08329682B2

反応ノート

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