反应详情

The combined mother liquors from the resolution of Intermediate T3 were concentrated under reduced pressure until no acetone remained and acidified to pH 3 with 0° C. 5N HCl. This solution was extracted 3 times with Et2O (200 ml portions) and the combined Et2O portions were washed successively with 1N HCl, H2O and brine, dried (MgSO4), filtered and concentrated under reduced pressure to give a yellow solid (71 g). This residue was recrystallized from hexane to give pure 5-fluoro-indan-1-carboxylic acid (Intermediate 2a, 58.6 g, 325.5 mmol) which was enriched in the R enantiomer. To Intermediate 2a in refluxing acetone (1 L) was added pulverized brucine (128.4 g, 325.5 mmol). After most solids had dissolved the solution was hot filtered and reheated to reflux as H2O (1 L) was added gradually. Excess acetone was boiled off until the solution became hazy. The solution was allowed to stand in a recrystallization dish for 1 month before solids appeared. The resultant solids were broken up, filtered off and recrystallized four more times in similar manner from acetone and H2O to give a buff colored solid which was taken up in 0° C. 1N HCl (150 ml). This solution was extracted 3 times with Et2O (75 ml portions) and the combined Et2O portions were washed successively with 1N HCl, H2O and brine, dried (MgSO4), filtered and concentrated under reduced pressure to give 6.13 g of (R)-5-fluoro-indan-1-carboxylic acid (Intermediate T4) as a pale solid which rotates sodium light at 20° C. with [α]20D+31.8 (c=4.49, benzene).

1. customThis residue was recrystallized from hexane
2. additionwas added
3. dissolutionAfter most solids had dissolved the solution
4. filtrationwas hot filtered
5. temperatureto reflux as H2O (1 L)
6. additionwas added gradually
7. waitto stand in a recrystallization dish for 1 month before solids
8. filtrationfiltered off
9. customrecrystallized four more times in similar manner from acetone and H2O
10. customto give a buff colored solid which
11. customwas taken up in 0° C
12. extractionThis solution was extracted 3 times with Et2O (75 ml portions)
13. washthe combined Et2O portions were washed successively with 1N HCl, H2O and brine
14. dry with materialdried (MgSO4)
15. filtrationfiltered
16. concentrationconcentrated under reduced pressure