Ammonia → HCID 86757967, compound

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).

1. concentrationThe reaction was concentrated under reduced pressure
2. dissolutionThe soft solid was dissolved with 25 mL of methylene chloride and suction
3. filtrationfiltered through a pad of flash grade silica gel
4. washeluted with 20% methylene chloride/hexanes
5. temperaturecooled to 10° C. in an ice bath
6. waitAfter 10 min
7. customthe cooling bath was removed
8. stirringAfter 30 minutes of stirring
9. customthe cooling bath was removed
10. stirringto stir for 1 h at room temperature
11. waitplaced under vacuum for 15 min
12. customThe material was used without purification
13. temperatureThe reaction temperature was increased to 125° C. for 150 min at which time the reaction
14. additionwas added
15. temperatureThis material (4.57 g,, 10.0 mmol) was cooled in an acetone/dry ice bath
16. customAfter 10 min the cooling bath was removed
17. temperatureto warm to room temperature
18. stirringstir for 16 h
19. concentrationThe reaction solution was concentrated under reduced pressure
20. dissolutiondissolved in 25 mL of a 9:1 mixture of acetone/water
21. waitto stand for 4 h
22. dry with materialThe reaction was dried with MgSO4, vacuum
23. filtrationfiltered
24. concentrationconcentrated under reduced pressure

ORD record

ord-0c6335f5f2fa4ad18d13cf2d96fa4b88

Source dataset

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06376548B1