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

HRID 4762

반응식

HRID 4762 반응식
[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]

참가 물질

5

반응물 3

HCID 79724-Methylmorpholine2회HCID 2733257Alanine methyl ester hydrochlorideHCID 13656657(S)-2-tert-Butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionic acid

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
-30 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5aa13ac42e5f4ec7a4920f45b70632bb
출처 데이터셋
uspto-grants-1988_02
특허 번호
US04727189

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