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

HRID 2176607

反応式

HRID 2176607 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-82c3476b83f249439222b0492062a27e
出典データセット
uspto-grants-2015_06
特許番号
US09066954B2

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