N-Fluorobenzenesulfonimide → Methyl 2-fluoro-2-(quinolin-6-yl)propanoate

HRID 2176607

반응식

HRID 2176607 반응식
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:37])(=O)=O)=CC=1>C1COCC1>[F:37][C:11]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:1]=[CH:2][CH:3]=[CH:4]2)([CH3:16])[C:12]([O:14][CH3:15])=[O:13]

참가 물질

5

반응물 3

HCID 588007N-FluorobenzenesulfonimideHCID 2733832Lithium HexamethyldisilazideHCID 57691200Methyl 2-(quinolin-6-YL)propanoate

생성물 1

HCID 67503402Methyl 2-fluoro-2-(quinolin-6-yl)propanoate수율 75.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a solution of methyl 2-(quinolin-6-yl)propanoate (0.868 g, 4.03 mmol) in THF (1.1M, 3.7 mL) at −78° C. was added LiHMDS (1M in THF) (5.24 ml, 5.24 mmol). The reaction was stirred at −78° C. for ˜15 minutes, then to it was added a solution of N-fluorobenzenesulfonimide (1.40 g, 4.44 mmol) in THF (1.0M, 4.5 mL). The reaction was allowed to warm to −10° C. over 2 h. The reaction was filtered through a plug of Celite, washed with EtOAc and the filtrate was then concentrated in vacuo. The concentrated material was rediluted with EtOAc and washed with saturated NH4Cl solution. The aqueous layer was then extracted with EtOAc, and the organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude material was dissolved in minimal DCM and purified via MPLC (eluting with isocratic 40% EtOAc:Hexanes to yield methyl 2-fluoro-2-(quinolin-6-yl)propanoate (0.709 g, 75.4% yield) as a yellow oil. To synthesize the corresponding acid, methyl 2-fluoro-2-(quinolin-6-yl)propanoate was saponified in a method similar to that of 2-(quinolin-6-yl)propanoic acid.

후처리

  1. temperatureto warm to −10° C. over 2 h
  2. filtrationThe reaction was filtered through a plug of Celite
  3. washwashed with EtOAc
  4. concentrationthe filtrate was then concentrated in vacuo
  5. additionThe concentrated material was rediluted with EtOAc
  6. washwashed with saturated NH4Cl solution
  7. extractionThe aqueous layer was then extracted with EtOAc
  8. dry with materialthe organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe crude material was dissolved in minimal DCM
  12. custompurified via MPLC (
  13. washeluting with isocratic 40% EtOAc

출처 및 근거

ORD 기록
ord-82c3476b83f249439222b0492062a27e
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09066954B2

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