反应详情
EQUATION
反应方程式
REACTANTS
反应物
Phosphoric trichloride
Cl3OP
Tetra-n-butylammonium fluoride
C16H36FN
N-{[(1,1-Dimethylethyl)oxy]carbonyl}-4-fluoro-beta-(4-fluorophenyl)-l-phenylalanine
C20H21F2NO4
4-Morpholinecarboxylic acid, 2-[2-(3-amino-5-fluoro-4-pyridinyl)ethyl]-5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-, 1,1-dimethylethyl ester, (2R,5S)-
C23H40FN3O4Si
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 0 °C
PROCEDURE
实验过程
POCl3 (0.579 mL, 6.21 mmol) was added to a solution of tert-Butyl (2R,5S)-2-[2-(3-amino-5-fluoropyridin-4-yl)ethyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate (2.65 g, 5.64 mmol) and N-(tert-butoxycarbonyl)-4-fluoro-β-(4-fluorophenyl)-L-phenylalanine [Patterson, D. E., et al. Org. Proc. Res. Dev. 2009, 13, 900-906.] (2.13 g, 5.64 mmol) in pyridine (28 mL) at −15° C. The reaction stirred for 30 min then warmed to 0° C. and stirred for 3 hours. The reaction was quenched with saturated aqueous KH2PO4, then brine and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure to afford a brown viscous oil. The resulting oil was dissolved in THF (28 mL) and a 1M solution of TBAF (11.3 mL, 11.3 mmol) in THF was added and the reaction stirred at ambient temperature overnight. The reaction was quenched with saturated aqueous KH2PO4 and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. Purification on silica gel (330 g) eluting with a gradient of 0-100% CHCl3 to 70:20:10 CHCl3/EtOAc/MeOH afforded the title compound (2.07 g, 2.90 mmol, 51% yield) as a white solid, MS (ESI): m/z=715.48 (MH+); 100% pure by LCMS.
WORKUP
后处理
- stirringstirred for 3 hours
- customThe reaction was quenched with saturated aqueous KH2PO4
- extractionbrine and the mixture was extracted with ethyl acetate (×3)
- dry with materialThe combined organic fractions were dried (MgSO4)
- filtrationfiltered
- customthe solvent was evaporated under reduced pressure
- customto afford a brown viscous oil
- stirringthe reaction stirred at ambient temperature overnight
- customThe reaction was quenched with saturated aqueous KH2PO4
- extractionthe mixture was extracted with ethyl acetate (×3)
- dry with materialThe combined organic fractions were dried (MgSO4)
- filtrationfiltered
- customthe solvent was evaporated under reduced pressure
- customPurification on silica gel (330 g)
- washeluting with a gradient of 0-100% CHCl3 to 70:20:10 CHCl3/EtOAc/MeOH