4-Methylmorpholine → t-butoxycarbonyl-2,6-dimethyl-D,L-tyrosyl-D-alanine, methyl ester

HRID 4762

反応式

HRID 4762 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20](O)=[O:21])[CH2:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([OH:18])=[CH:13][C:12]=1[CH3:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.Cl.[CH3:31][O:32][C:33](=[O:37])[C@H:34]([CH3:36])[NH2:35]>C(Cl)Cl>[CH3:2][C:1]([CH3:3])([O:5][C:6]([NH:8][CH:9]([C:20]([NH:35][C@@H:34]([C:33]([O:32][CH3:31])=[O:37])[CH3:36])=[O:21])[CH2:10][C:11]1[C:12]([CH3:19])=[CH:13][C:14]([OH:18])=[CH:15][C:16]=1[CH3:17])=[O:7])[CH3:4]

参加物

5

反応物 3

HCID 79724-Methylmorpholine2 回HCID 2733257Alanine methyl ester hydrochlorideHCID 13656657(S)-2-tert-Butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionic acid

生成物 1

HCID 14620778t-butoxycarbonyl-2,6-dimethyl-D,L-tyrosyl-D-alanine, methyl ester収率 98.9%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-30 °C

実験手順

Racemic t-butoxycarbonyl 2,6-dimethyltyrosine (3.9 g, 10 mmoles) was dissolved in 30 ml of CH2Cl2 by adding 1.12 ml (10 mmoles) of NMM. After bringing this mixture to reflux it was cooled to -30° C. and 1.32 ml (10 mmoles) of IBCF were added to this stirred solution. The temperature was allowed to rise to -15° C. and then lowered to -50° C. (D) alanine methyl ester hydrochloride (1.54 g, 11 mmoles) was added to the solution followed by 1.3 ml (11 mmoles) of NMM. The mixture was allowed to warm to room temperature and stand for 16 hours. The majority of the CH2Cl2 was removed under reduced pressure. Ethyl acetate (200 ml) was added and this solution was washed twice with 100 ml portions of 0.5 molar KHSO4, once with 100 ml of H2O and dried over MgSO4. Removal of all solvent gave 3.9 g of the mixture of diastereomers. Recrystallization of this material from Skelly B/CH2Cl2 produced 1.6 g (4.2 mmoles) of diastereomer F. Removal of the solvent from the filtrate gave 1.3 g (3.3 mmoles) of diastereomer S contaminated by less than 10% of diastereomer F.

後処理

  1. temperatureto reflux it
  2. addition1.32 ml (10 mmoles) of IBCF were added to this stirred solution
  3. customto rise to -15° C.
  4. customlowered to -50° C.
  5. additionwas added to the solution
  6. temperatureto warm to room temperature
  7. customThe majority of the CH2Cl2 was removed under reduced pressure
  8. additionEthyl acetate (200 ml) was added
  9. washthis solution was washed twice with 100 ml portions of 0.5 molar KHSO4, once with 100 ml of H2O
  10. dry with materialdried over MgSO4
  11. customRemoval of all solvent

出典と根拠

ORDレコード
ord-5aa13ac42e5f4ec7a4920f45b70632bb
出典データセット
uspto-grants-1988_02
特許番号
US04727189

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