Hydrochloric Acid → 1H-Indole-1-acetic acid

HRID 900364

반응식

HRID 900364 반응식
N1C2C(=CC=CC=2)C=C1.[H-].[Na+].C(OC(=O)CBr)C.C([O:21][C:22](=[O:33])[CH2:23][N:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25]1)C.[OH-].[Na+].Cl>CN(C=O)C.CO.C1COCC1.ClCCl>[N:24]1([CH2:23][C:22]([OH:33])=[O:21])[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25]1

참가 물질

11

반응물 6

HCID 313Hydrochloric AcidHCID 798IndoleHCID 7748Ethyl bromoacetateHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 967684Indol-1-yl-acetic acid ethyl ester

생성물 1

HCID 904481H-Indole-1-acetic acid

시약·촉매·용매 4

HCID 887Methanol용매2회HCID 6228Dimethylformamide용매2회HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
70 °C

실험 절차

1H-indole (5.0 g, 42.7 mmol) in anhydrous DMF (10 mL) was added to a suspension of sodium hydride (1.13 g, 46.9 mmol) in anhydrous DMF (20 mL) in a flame dried flask at 0° C. stirred under nitrogen atmosphere. Fifteen minutes after gas evolution had ceased, bromo-acetic acid ethyl ester (5.7 mL, 51.2 mmol) was added and the reaction was heated to 70° C. and stirred under nitrogen. Upon completion (TLC: 50% dichloromethane in heptane), the reaction mixture was quenched with water (50 mL) and extracted with diethyl ether (3×50 mL). The combined extract was washed sequentially with water and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. To a solution of crude indol-1-yl-acetic acid ethyl ester (9.37 g, 46.2 mmol) in methanol (20 mL) and THF (80 mL) was added 6N NaOH solution (25 mL). Upon completion (TLC: 10% methanol in dichloromethane), the mixture was acidified with 6N HCl solution to pH 2, and extracted with ethyl acetate (3×75 mL). The combined extract was washed sequentially with water and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to yield the crude titled compound as a light brown solid. 1H NMR (DMSO-d6, 300 MHz) δ 7.51 (1H, dd, J=8, 1 Hz, Ar—H), 7.35 (1H, dd, J=8, 1 Hz, Ar—H), 7.30 (1H, d, J=3 Hz, Ar—H), 7.09 (1H, td, J=7.5, 1 Hz, Ar—H), 6.99 (1H, td, J=7.5, 1 Hz, Ar—H), 6.41 (1H, dd, J=3, 1 Hz, Ar—H), 4.99 (2H, s, CH2).

후처리

  1. customdried flask at 0° C.
  2. customFifteen minutes
  3. stirringstirred under nitrogen
  4. customUpon completion (TLC: 50% dichloromethane in heptane), the reaction mixture was quenched with water (50 mL)
  5. extractionextracted with diethyl ether (3×50 mL)
  6. extractionThe combined extract
  7. washwas washed sequentially with water and brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. extractionextracted with ethyl acetate (3×75 mL)
  12. extractionThe combined extract
  13. washwas washed sequentially with water and brine
  14. dry with materialdried over anhydrous MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-fa4f8cd225fb428fb6124e18dc67f499
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07358248B2

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