反应 #2122512

反应方程式

(1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid t-butyl ester

oxalic acid

oxalate

→

(1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid t-butyl ester oxalic acid

收率 84.6%

溶剂

t-butyl acetate

2-propanol

反应条件

后处理

1. 1
   workup.ADDITIONcharged to a 3 L four-neck flask
2. 2
   其他equipped with overhead mechanical stirring
3. 3
   workup.ADDITIONa thermometer, addition funnel
4. 4
   温度reflux condenser
5. 5
   温度increasing the mixture's temperature to 31° C
6. 6
   其他to precipitate
7. 7
   workup.ADDITIONafter addition of ˜50 mL of the oxalic acid solution
8. 8
   其他resulted in a thick suspension
9. 9
   workup.ADDITIONafter the addition of 450 mL
10. 10
    workup.DISSOLUTIONthe precipitated solids redissolved
11. 11
    其他to provide a dark yellow solution
12. 12
    其他Solids precipitated again rapidly
13. 13
    workup.ADDITIONafter the addition of 600 mL of the oxalic solution
14. 14
    workup.ADDITIONpersisted through the end of the oxalic acid addition
15. 15
    温度This suspension was then heated 78° C.
16. 16
    其他to provide a thin suspension which
17. 17
    温度to cool passively
18. 18
    workup.STIRRINGwith stirring to ambient temperature (˜21° C.)
19. 19
    过滤the precipitated solids were collected by filtration
20. 20
    洗涤washed successively with isopropanol (450 mL), isopropyl acetate (450 mL), and methyl t-butyl methyl ether (450 mL)
21. 21
    干燥The solids were dried in a vacuum oven (30° C., 25″ vacuum, N2 stream)

实验过程

97.9 g (463.3 mmol) of (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid t-butyl ester from the two preparations according to Step 1 were dissolved in 750 mL t-butyl acetate and charged to a 3 L four-neck flask equipped with overhead mechanical stirring, a thermometer, addition funnel, and reflux condenser. With stirring at ambient temperature (˜21° C.), a solution of 44.0 g (488.6 mmol) of oxalic acid in 750 mL 2-propanol was added dropwise over 37 minutes, increasing the mixture's temperature to 31° C. Solids began to precipitate after addition of ˜50 mL of the oxalic acid solution, and resulted in a thick suspension after the addition of 450 mL. After addition of 500 mL of the oxalate solution, the precipitated solids redissolved to provide a dark yellow solution. Solids precipitated again rapidly after the addition of 600 mL of the oxalic solution and persisted through the end of the oxalic acid addition. This suspension was then heated 78° C. to provide a thin suspension which was allowed to cool passively with stirring to ambient temperature (˜21° C.). After 16 hours since the cooling began, the precipitated solids were collected by filtration and washed successively with isopropanol (450 mL), isopropyl acetate (450 mL), and methyl t-butyl methyl ether (450 mL). The solids were dried in a vacuum oven (30° C., 25″ vacuum, N2 stream) to provide 118.1 g (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid t-butyl ester oxalic acid 1:1 salt (64% yield from (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid hydrochloride) as a dense, tan free flowing powder (99.7% purity by GC analysis), which exhibited the expected 1H-NMR spectrum for (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid t-butyl ester oxalic acid (1:1) salt.

来源