Dimethylformamide → tert-Butyl 3-formyl-5-phenylpyridin-2-ylcarbamate

HRID 2221087노트

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HRID 2221087 반응식
[C:1]1([C:7]2[CH:8]=[CH:9][C:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(CCN(C)C)C.C([Li])CCC.CN([CH:37]=[O:38])C>C1COCC1>[CH:37]([C:9]1[C:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[N:11][CH:12]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=1)=[O:38]

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 58671538tert-Butyl 5-phenylpyridin-2-ylcarbamateHCID 178418339Butyllithium

생성물 1

HCID 58671547tert-Butyl 3-formyl-5-phenylpyridin-2-ylcarbamate수율 42%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-72 °C

실험 절차

A solution of 1C (2.40 g, 8.88 mmol) in dry THF (35 mL) and TMEDA (3.35 mL, 22.2 mmol) under argon was cooled to −72° C. and treated dropwise with n-butyllithium (2.5 M in hexanes, 8.9 mL, 22.2 mmol) at such a rate so that the temperature did not exceed −65° C. Upon completion of the addition, the reaction was stirred at −72° C. for an additional 15 min and then at −20° C. for 1.5 h. The reaction was cooled again to −72° C., and dry DMF (1.4 mL, 17.8 mmol) was added while the temperature was maintained below −65° C. The mixture was allowed to stir at RT for 30 min. After this time, no starting material was detected by LC-MS. The solution was cooled to 0° C. and quenched by the addition of 1 M aqueous HCl to bring the pH to 6-8. The reaction was stirred at RT for 15 min, extracted with EtOAc (3×100 mL). The combined organic layers were washed with saturated NaCl, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by silica gel (110 g) column chromatography, eluting with a gradient of EtOAc (0-100%) in hexane to give the title compound as a yellow solid (1.1 g, 42%). LC/MS (method A): retention time=3.43 min, (M+H−tBu)+=243.

후처리

  1. customdid not exceed −65° C
  2. additionUpon completion of the addition
  3. waitat −20° C. for 1.5 h
  4. temperatureThe reaction was cooled again to −72° C.
  5. temperaturewas maintained below −65° C
  6. stirringto stir at RT for 30 min
  7. temperatureThe solution was cooled to 0° C.
  8. customquenched by the addition of 1 M aqueous HCl
  9. stirringThe reaction was stirred at RT for 15 min
  10. extractionextracted with EtOAc (3×100 mL)
  11. washThe combined organic layers were washed with saturated NaCl
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. customevaporated under reduced pressure
  15. customThe residue was purified by silica gel (110 g) column chromatography
  16. washeluting with a gradient of EtOAc (0-100%) in hexane

출처 및 근거

ORD 기록
ord-1082cf48995a428aac2ba15939eb6fd9
출처 데이터셋
uspto-grants-2008_05
특허 번호
US07368458B2

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