Hydrochloric Acid → 5-Fluoro-indan-2-carboxylic acid methyl ester

HRID 9277

반응식

HRID 9277 반응식
[H-].[Na+].[CH3:3][O:4][C:5](=[O:8])OC.[F:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[C:15](=O)[CH2:14][CH2:13]2.Cl>C1COCC1>[CH3:3][O:4][C:5]([CH:14]1[CH2:13][C:12]2[C:16](=[CH:17][CH:18]=[C:10]([F:9])[CH:11]=2)[CH2:15]1)=[O:8]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 12021Dimethyl CarbonateHCID 24758Sodium hydrideHCID 1365375-Fluoro-1-indanone

생성물 1

HCID 669988455-Fluoro-indan-2-carboxylic acid methyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
65 °C

실험 절차

To a mixture of NaH (2.64 g, 66 mmol) in dimethylcarbonate (4.2 mL, 50 mmol) in THF (30 mL) was added a solution of 5-fluoroindanone (commercially available from Aldrich) (5 g, 33 mmol). After 30 m at 65° C. the mixture was cooled to rt, acidified with HCl (aq) and extracted with Et2O or EtOAc. The organic layers were washed with water, dried over MgSO4 and evaporated to dryness. The residue was used in the next step without further purification. The keto-ester was dissolved in AcOH (100 mL) and 70% perchloric acid (2 mL). 10% Pd/C (2 g) was added and the mixture was hydrogenated at 50 psi for 18 h. The mixture was diluted with Et2O or CHCl3 and water and filtered through a pad of celite. The organic layer was separated and the aqueous layer was extracted with Et2O. The organic fractions were pooled, washed with water, dried over MgSO4, filtered and evaporated to leave a residue. The residue was purified by chromatography on silica gel with 15% EtOAc: hexane to give 5-fluoro-indan-2-carboxylic acid methyl ester (Intermediate EIGHTEEN-3), 2.25 g. Use of 5-fluoro-indan-2-carboxylic acid methyl ester (Intermediate EIGHTEEN-3) in Method SEVENTEEN produced 4-(5-fluoro-indan-2-yl)-1,3-dihydro-imidazole-2-thione (Compound 145).

후처리

  1. extractionextracted with Et2O or EtOAc
  2. washThe organic layers were washed with water
  3. dry with materialdried over MgSO4
  4. customevaporated to dryness
  5. customThe residue was used in the next step without further purification
  6. dissolutionThe keto-ester was dissolved in AcOH (100 mL)
  7. addition10% Pd/C (2 g) was added
  8. additionThe mixture was diluted with Et2O or CHCl3 and water
  9. filtrationfiltered through a pad of celite
  10. customThe organic layer was separated
  11. extractionthe aqueous layer was extracted with Et2O
  12. washwashed with water
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. customevaporated
  16. customto leave a residue
  17. customThe residue was purified by chromatography on silica gel with 15% EtOAc

출처 및 근거

ORD 기록
ord-21761f62448e4eaeb88a57c0e17395ff
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091232B2

연결된 노트

불러오는 중…