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

Temperatur

-30 °C

Racemic t-butoxycarbonyl 2,6-dimethyltyrosine (3.9 g, 10 mmol) was dissolved in 30 ml of CH2Cl2 by adding 1.12 ml (10 mmol) of NMM. After bringing this mixture to reflux it was cooled to -30° C. and 1.32 ml (10 mmol) 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 mmol) was added to the solution followed by 1.3 ml (11 mmol) of NMM. The mixture was allowed to warm to room temperature and stand for 16 h. The majority of the CH2Cl2 was removed under reduced pressure. Ethyl acetate (EtOAc, 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(hexanes)/CH2Cl2 produced 1.6 g (4.2 mmol) of diastereomer F. Removal of the solvent from the filtrate gave 1.3 g (3.3 mmol) of diastereomer S contaminated by less tha 10% of diastereomer DF. The mixture of diastereomers or either of the separated diastereomers were used in subsequent examples without further purification.

1. temperatureto reflux it
2. addition1.32 ml (10 mmol) 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 (EtOAc, 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

ORD-Eintrag

ord-cfaf8c27603f4d04aa7f5cdeb4bb552c

Quelldatensatz

uspto-grants-1990_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04933325