반응 #2122512

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(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

수율 84.6%

용매

t-butyl acetate

2-propanol

반응 조건

후처리

1. 1
   workup.ADDITIONcharged to a 3 L four-neck flask
2. 2
   기타equipped with overhead mechanical stirring
3. 3
   workup.ADDITIONa thermometer, addition funnel
4. 4
   온도reflux condenser
5. 5
   온도increasing the mixture's temperature to 31° C
6. 6
   기타to precipitate
7. 7
   workup.ADDITIONafter addition of ˜50 mL of the oxalic acid solution
8. 8
   기타resulted in a thick suspension
9. 9
   workup.ADDITIONafter the addition of 450 mL
10. 10
    workup.DISSOLUTIONthe precipitated solids redissolved
11. 11
    기타to provide a dark yellow solution
12. 12
    기타Solids 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
    온도This suspension was then heated 78° C.
16. 16
    기타to provide a thin suspension which
17. 17
    온도to cool passively
18. 18
    workup.STIRRINGwith stirring to ambient temperature (˜21° C.)
19. 19
    여과the precipitated solids were collected by filtration
20. 20
    세척washed successively with isopropanol (450 mL), isopropyl acetate (450 mL), and methyl t-butyl methyl ether (450 mL)
21. 21
    건조The solids were dried in a vacuum oven (30° C., 25″ vacuum, N2 stream)

실험 절차

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.

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