Hydrochloric Acid → (R)-5-fluoro-indan-1-carboxylic acid

HRID 9300노트

반응식

HRID 9300 반응식
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([C:11]([OH:13])=[O:12])[CH2:6][CH2:5]2.COC1C=C2[C@@]34[C@@H]5C[C@H]6C(CN5CC3)=CCO[C@H]3CC(=O)N([C@H]4[C@@H]63)C2=CC=1OC.Cl>CC(C)=O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([C:11]([OH:13])=[O:12])[CH2:6][CH2:5]2

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 442021BrucineHCID 219861185-fluoro-2,3-dihydro-1H-indene-1-carboxylic acid3회

생성물 1

HCID 58681402(R)-5-fluoro-indan-1-carboxylic acid수율 10.5%

시약·촉매·용매 1

HCID 180Acetone용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-bd97467992de4fa6b98437d8bbc8d45d
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091232B2

반응 노트

불러오는 중…