Methanol → 6-Chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid

HRID 1421582노트

반응식

HRID 1421582 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18]CC)=[O:17])=[CH:5]2.[OH-].[Na+].CO.O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]([F:15])([F:13])[F:14])[C:6]([C:16]([OH:18])=[O:17])=[CH:5]2

참가 물질

6

반응물 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium HydroxideHCID 21883646Ethyl 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate

생성물 1

HCID 100163706-Chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid수율 41.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

The ester from Step 2 (1.7 g, 5.6 mmol) and 2.5 N sodium hydroxide (4.4 mL, 11 mmol) were mixed in tetrahydrofuran (25 mL), methanol (10 mL), and water (25 mL). After stirring overnight, contents were concentrated in vacuo to remove the THF and methanol. The aqueous solution remaining was extracted with diethyl ether (2×100 mL). The resulting aqueous layer was acidified with 2 N HCl causing the precipitation of an oil. The oil was purified by flash chromatography on silica gel, eluting with ethyl acetate-hexanes (1:1). Fractions containing the desired product were combined, and concentrated in vacuo. The residue was triturated with dichloromethane, and filtered to afford the 6-chloro-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylic acid as a yellow solid (0.645 g, 41%): mp 187.8-188.8° C. 1H NMR (acetone-d6, 300 MHz) 7.69 (s, 1H), 7.36 (s, 1H), 7.15 (d, 1H, J=8.0 Hz), 6.83 (d, 1H, J=8.0 Hz), 6.60 (brs, 1H), 5.20 (m, 1H). ESHRMS m/z 276.0040 (M-H, Calc'd 276.0039). Anal. Calc'd for C11H7NO2F3Cl+2.6% H2O: C, 46.39; H, 2.98; N, 4.92. Found: C, 45.99; H, 2.54; N, 4.85.

후처리

  1. concentrationcontents were concentrated in vacuo
  2. customto remove the THF and methanol
  3. extractionThe aqueous solution remaining was extracted with diethyl ether (2×100 mL)
  4. customthe precipitation of an oil
  5. customThe oil was purified by flash chromatography on silica gel
  6. washeluting with ethyl acetate-hexanes (1:1)
  7. additionFractions containing the desired product
  8. concentrationconcentrated in vacuo
  9. customThe residue was triturated with dichloromethane
  10. filtrationfiltered

출처 및 근거

ORD 기록
ord-ab4809cf8ed74424807c60d8efbde23a
출처 데이터셋
uspto-grants-2000_06
특허 번호
US06077850

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