反応 #930276

反応方程式

chloroformate

3,3-dimethylbutyric acid

diisopropylethylamine

3,3-dimethylbutyric acid ethylsulfanylcarbonyloxymethyl ester

ammonia

Sulfuryl chloride

phosphonomethyl glycine

hexamethyldisilazane

→

desired product

収率 101.2%

3,3-Dimethylbutyric acid (carboxymethyl phosphonomethylcarbamoyloxy)-methyl ester

収率 101.2%

溶媒

THF

methylene chloride

反応条件

後処理

1. 1
   濃縮The reaction was concentrated under reduced pressure
2. 2
   workup.DISSOLUTIONThe soft solid was dissolved with 25 mL of methylene chloride and suction
3. 3
   ろ過filtered through a pad of flash grade silica gel
4. 4
   洗浄eluted with 20% methylene chloride/hexanes
5. 5
   温度cooled to 10° C. in an ice bath
6. 6
   workup.WAITAfter 10 min
7. 7
   その他the cooling bath was removed
8. 8
   workup.STIRRINGAfter 30 minutes of stirring
9. 9
   その他the cooling bath was removed
10. 10
    workup.STIRRINGto stir for 1 h at room temperature
11. 11
    workup.WAITplaced under vacuum for 15 min
12. 12
    その他The material was used without purification
13. 13
    温度The reaction temperature was increased to 125° C. for 150 min at which time the reaction
14. 14
    workup.ADDITIONwas added
15. 15
    温度This material (4.57 g,, 10.0 mmol) was cooled in an acetone/dry ice bath
16. 16
    その他After 10 min the cooling bath was removed
17. 17
    温度to warm to room temperature
18. 18
    workup.STIRRINGstir for 16 h
19. 19
    濃縮The reaction solution was concentrated under reduced pressure
20. 20
    workup.DISSOLUTIONdissolved in 25 mL of a 9:1 mixture of acetone/water
21. 21
    workup.WAITto stand for 4 h
22. 22
    乾燥The reaction was dried with MgSO4, vacuum
23. 23
    ろ過filtered
24. 24
    濃縮concentrated under reduced pressure

実験手順

To a stirred ice cold solution of O-iodomethyl S-ethyl carbothioate (5.80 g, 23.6 mmol) in 60 mL of dry THF was added 3,3-dimethylbutyric acid (3.56 g, 30.7 mmol) followed by diisopropylethylamine (3.90 g, 30.2 mmol). The reaction was allowed to stir at room temperature for 16 h. The reaction was concentrated under reduced pressure. The soft solid was dissolved with 25 mL of methylene chloride and suction filtered through a pad of flash grade silica gel and eluted with 20% methylene chloride/hexanes. The material was carried on directly to the next step. A 100 mL roundbottom flask was charged with the 3,3-dimethylbutyric acid ethylsulfanylcarbonyloxymethyl ester (4.4 g1, 8.8 mmol) and cooled to 10° C. in an ice bath. Sulfuryl chloride (3.04 g, 22.6 mmol) was added over one minute. After 10 min, the cooling bath was removed. After 30 minutes of stirring, the cooling bath was removed, and the reaction was allowed to stir for 1 h at room temperature and then placed under vacuum for 15 min. The material was used without purification. In a separate flask, a stirred solution of phosphonomethyl glycine (1.69 g, 10 mmol) in hexamethyldisilazane (4.4 mL, 3.4 g, 21 mmol) was slowly heated to 90° C. (at this temperature it was noted out gassing of ammonia occurred). The reaction temperature was increased to 125° C. for 150 min at which time the reaction became homogeneous. The solution was allowed to cool to room temperature at which time, dry methylene chloride (10 mL) was added. This material (4.57 g,, 10.0 mmol) was cooled in an acetone/dry ice bath. The generated chloroformate (1.95 g, 9.33 mmol) was added by syringe to the silylated phosphonomethylglycine solution. After 10 min the cooling bath was removed and the reaction was allowed to warm to room temperature and stir for 16 h. The reaction solution was concentrated under reduced pressure and dissolved in 25 mL of a 9:1 mixture of acetone/water and allowed to stand for 4 h. The reaction was dried with MgSO4, vacuum filtered, and concentrated under reduced pressure. The solid was triterated twice with 60 mL of warm hexanes and then placed under vacuum to afford the desired product (3.04 g) in 96% yield. 1H-NMR (300 MHz, D2O) δ (ppm): 1H-NMR 0.86 (s, 9H), 2.16 (d, 2H), 3.52 (dd, 2H), 4.10 (d, 2H), 5.61 (d, 2H).

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