反応 #57036

反応方程式

brucine

Intermediate 2a

5-fluoro-indan-1-carboxylic acid

5-fluoro-indan-1-carboxylic acid

Intermediate 2a

5-fluoro-indan-1-carboxylic acid

HCl

→

(R)-5-fluoro-indan-1-carboxylic acid

収率 10.5%

溶媒

acetone

反応条件

後処理

1. 1
   その他This residue was recrystallized from hexane
2. 2
   workup.ADDITIONwas added
3. 3
   workup.DISSOLUTIONAfter most solids had dissolved the solution
4. 4
   ろ過was hot filtered
5. 5
   温度to reflux as H2O (1 L)
6. 6
   workup.ADDITIONwas added gradually
7. 7
   workup.WAITto stand in a recrystallization dish for 1 month before solids
8. 8
   ろ過filtered off
9. 9
   その他recrystallized four more times in similar manner from acetone and H2O
10. 10
    その他to give a buff colored solid which
11. 11
    その他was taken up in 0° C
12. 12
    抽出This solution was extracted 3 times with Et2O (75 ml portions)
13. 13
    洗浄the combined Et2O portions were washed successively with 1N HCl, H2O and brine
14. 14
    乾燥dried (MgSO4)
15. 15
    ろ過filtered
16. 16
    濃縮concentrated under reduced pressure

実験手順

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).

出典