反应 #1244312

反应方程式

sodium chloride

N-Boc-glycine methyl ester

diisopropylamine

n-BuLi

ethyl (fluoromethyl)(1,1-diethoxyethyl)phosphinate

acetic acid

→

ethyl (3-(N-(tert-butoxycarbonyl) amino)-1-fluoro-2-oxopropyl)(1,1-diethoxyethyl)phosphinate

收率 44.6%

溶剂

THF

THF

THF

反应条件

后处理

1. 1
   workup.ADDITIONAfter the addition the reaction mixture
2. 2
   温度was maintained below −70° C
3. 3
   workup.ADDITIONAfter the addition
4. 4
   workup.STIRRINGwas stirred at −78° C. for 1 h
5. 5
   温度warmed to room temperature
6. 6
   其他the organic phase separated
7. 7
   萃取The aqueous phase was then extracted with ethyl acetate (2×75 mL)
8. 8
   干燥The combined organic phase was dried over anhydrous sodium sulfate
9. 9
   浓缩concentrated under reduced pressure
10. 10
    其他affording the crude product as a pale yellow oil (2.69 g)
11. 11
    其他The crude product was purified by column chromatography (2×35 cm column)
12. 12
    洗涤eluting with 40% ethyl acetate in hexane

实验过程

To a solution of diisopropylamine (2.5 mL, 14.5 mmol, 3.5 eq) in THF (30 mL) at −10° C. was added dropwise (about 10 minutes) n-BuLi (1.4 M in hexanes, 9.0 mL, 14.5 mmol). After 10 minutes, the reaction was cooled to −78° C., and a solution of ethyl (fluoromethyl)(1,1-diethoxyethyl)phosphinate (2.0 g, 8.26 mmol, 2 eq) in THF (10 mL) was added dropwise over 10 minutes. After the addition the reaction mixture was stirred at −78° C. for 1 h. A solution of N-Boc-glycine methyl ester (0.8 g, 4.1 mmol) in THF (10 mL) was added dropwise over 10 minutes such that the internal temperature was maintained below −70° C. After the addition was complete the reaction was stirred at −78° C. for 1 h. The reaction was quenched with acetic acid (1 mL, 14.5 mmol) and then warmed to room temperature. Saturated aqueous sodium chloride (75 mL) was added to the reaction and the organic phase separated. The aqueous phase was then extracted with ethyl acetate (2×75 mL). The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure affording the crude product as a pale yellow oil (2.69 g). The crude product was purified by column chromatography (2×35 cm column), eluting with 40% ethyl acetate in hexane. This method afforded ethyl (3-(N-(tert-butoxycarbonyl) amino)-1-fluoro-2-oxopropyl)(1,1-diethoxyethyl)phosphinate as a clear colorless oil (0.73 g, 44%). 1H NMR (300 MHz, CDCl3) δ 5.78-5.24 (m,2H), 4.52-4.08 (m, 4H), 3.94-3.50 (m, 4H), 1.62-1.51 (m, 3H), 1.50-1.32 (m, 3H), 1.42 (s, 9H), 1.30-1.12 (m, 6H).

来源