Cesium carbonate → tert-butyl (1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

HRID 870923노트

반응식

HRID 870923 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[CH2:9][O:8][C:6]=2[CH:7]=1.[OH:16][CH2:17][C@@H:18]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19][CH:20]([CH3:22])[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH:14]1[CH:13]=[N:12][CH:11]=[C:10]2[CH2:9][O:8][C:6]3[CH:7]=[C:2]([O:16][CH2:17][CH:18]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:29])[CH3:28])[CH2:19][CH:20]([CH3:22])[CH3:21])[CH:3]=[CH:4][C:5]=3[C:15]=12

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 7018766Boc-L-leucinolHCID 866958928-chloro-5H-chromeno[3,4-c]pyridine

생성물 1

HCID 86724429tert-butyl (1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate수율 45%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

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온도
80 °C

실험 절차

To 8-chloro-5H-chromeno[3,4-c]pyridine (0.489 g, 2.247 mmol) (prepared as in Example 5, Part D), (S)-tert-butyl (1-hydroxy-4-methylpentan-2-yl)carbamate (1.474 g, 6.79 mmol), di-tert-butyl(2′,4′,6′-triisopropyl-[1′,1′-biphenyl]-2-yl)phosphine (0.572 g, 1.348 mmol), palladium (II) acetate (0.151 g, 0.674 mmol) and cesium carbonate (1.098 g, 3.37 mmol) was added toluene (4 mL). Nitrogen gas was bubbled through the mixture for 5 min and the mixture heated at 80° C. for 15 h. The reaction mixture was cooled to room temperature and filtered through a bed of celite. Water (10 mL) was added to the filtrate and the product was extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with brine (1×10 mL), dried with sodium sulfate and concentrated under reduced pressure. The residue so obtained was purified by preparative TLC using (50% ethyl acetate in pet ether) to afford tert-butyl (1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.4 g, 1.00 mmol, 45% yield) as a semi solid. LCMS (ESI) m/e 399.2 [(M+H)1, calcd for C23H31N2O4 399.5]; LC/MS retention time (Method C): tR=2.16 min.

후처리

  1. customNitrogen gas was bubbled through the mixture for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through a bed of celite
  4. additionWater (10 mL) was added to the filtrate
  5. extractionthe product was extracted with ethyl acetate (3×15 mL)
  6. washThe combined organic extracts were washed with brine (1×10 mL)
  7. dry with materialdried with sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue so obtained
  10. customwas purified by preparative TLC

출처 및 근거

ORD 기록
ord-8c0d7ad869e4405fbcf01d7175270d38
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969564B2

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