반응 #83658

반응 방정식

2(R,S)-methylthiazolidine-4(R)-carboxylic acid

N-phthaloyl-L-glutamic anhydride

phthalhydrazide

bis-(trimethylsilyl)trifluoroacetamide

→

desired product

3-(γ-L-Glutamyl)-2(R,S)-Methylthiazolidine-4(R)-Carboxylic Acid

용매

CH3CN

CH3CN

Et3N

H2O

반응 조건

후처리

1. 1
   기타prepared
2. 2
   온도the mixture was heated
3. 3
   온도under reflux for 1.25 hours
4. 4
   workup.DISSOLUTIONThe solids dissolved within 10 minutes
5. 5
   온도of heating
6. 6
   workup.ADDITIONwas added
7. 7
   기타After 5 days at room temperature the solvent was evaporated in vacuo
8. 8
   workup.ADDITIONTo the resultant pale yellow thick oil (41.1 g) were added
9. 9
   workup.STIRRINGAfter 2 days of stirring the solvent
10. 10
    기타was evaporated in vacuo
11. 11
    기타the solvent evaporated again
12. 12
    기타to give 49.7 g of a thick, white oil
13. 13
    workup.ADDITIONThis was poured
14. 14
    기타The resultant precipitate of phthalhydrazide was removed by filtration
15. 15
    세척the filter cake was rinsed with H2O (approximately 100 mL)
16. 16
    기타precipitated
17. 17
    기타This was removed by filtration
18. 18
    기타the filtrate was evaporated in vacuo
19. 19
    기타under 40° C.
20. 20
    기타to give 35.8 g of a thick, pale yellow oil whose NMR spectrum

실험 절차

To a stirred suspension of 2(R,S)-methylthiazolidine-4(R)-carboxylic acid (8.51 g, 57.9 mmol) prepared according to Nagasawa et al., J. Med. Chem., 27, 591 (1984), which is incorporated herein by reference, in dry CH3CN (100 mL) under a N2 atmosphere was added bis-(trimethylsilyl)trifluoroacetamide (17.0 mL, 17.7 g, 68.7 mmol, obtained from Sigma Chemical Co., "BSTFA") and the mixture was heated under reflux for 1.25 hours. The solids dissolved within 10 minutes of heating. After cooling to room temperature, N-phthaloyl-L-glutamic anhydride (15.0 g, 58.0 mmol) prepared according to Elbefling et al., Org. Prep. Proceed. Int., 11, 67 (1979), which is incorporated herein by reference, was added, followed by dry CH3CN (25 mL). After 5 days at room temperature the solvent was evaporated in vacuo. To the resultant pale yellow thick oil (41.1 g) were added with stirring under a N2 atmosphere, 1.0M Et3N in CH3OH (220 mL) and 2.0M NH2NH2.H2O in 50% aqueous CH3OH (73 mL). After 2 days of stirring the solvent was evaporated in vacuo. The resultant thick, white, semisolid (51.8 g) was suspended in H2O (150 mL) and the solvent evaporated again to give 49.7 g of a thick, white oil. This was poured into warm H2O (350 mL) with swirling. The resultant precipitate of phthalhydrazide was removed by filtration and the filter cake was rinsed with H2O (approximately 100 mL). The combined filtrate was acidified to pH 3.5 with 1.0N HCl, whereupon more phthalhydrazide precipitated. This was removed by filtration, and the filtrate was evaporated in vacuo, keeping the temperature under 40° C., to give 35.8 g of a thick, pale yellow oil whose NMR spectrum showed the presence of much Et3N and some phthalhydrazide in addition to the desired product. The oil was, therefore, resuspended in H2O (75 mL), the mixture was stirred, and the additional solids that precipitated were removed by filtration. The filtrate was evaporated to incipient dryness in vacuo to give a thick oil (24.6 g).

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