Ethyl Acetate → 2-{7-[(4-Fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol

HRID 513960노트

반응식

HRID 513960 반응식
FC1C=CC(C[O:7][C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13](C(OCC)=O)[CH:14]=[N:15]3)=[N:10][CH:9]=2)=CC=1.O[C:26]1C=C2C(C=C(C(OCC)=O)C=N2)=NC=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52]Cl)=[CH:50][CH:49]=1.CCO[C:59]([CH3:61])=[O:60]>CN(C=O)C.O>[F:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][O:7][C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([C:59]([OH:60])([CH3:61])[CH3:26])[CH:14]=[N:15]3)=[N:10][CH:9]=2)=[CH:50][CH:49]=1

참가 물질

8

반응물 5

HCID 8857Ethyl AcetateHCID 96024-Fluorobenzyl chlorideHCID 10796Cesium carbonateHCID 90418013Ethyl 7-((4-fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylateHCID 136227102Ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate2회

생성물 1

HCID 863016572-{7-[(4-Fluorophenyl)methoxy]-1,5-naphthyridin-3-yl}propan-2-ol수율 67%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

Ethyl 7-((4-fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylate. To a solution of ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate (Intermediate 4, 3.0 g, 13.75 mmol) in DMF (70 mL) was added Cs2CO3 (8.96 g, 0.03 mol), followed by 4-fluorobenzyl chloride (2.42 mL, 0.02 mol). The reaction was stirred at ambient temperature for 72 h. The crude reaction mixture was poured into EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic fractions were washed with brine and concentrated under reduced pressure onto silica. Purification (FCC, SiO2, 0-60%, EtOAc/hexanes) afforded the title compound as a white solid (3.0 g, 67%) 1H NMR (400 MHz, CDCl3) δ 9.45 (d, J=1.6 Hz, 1H), 8.97 (s, 1H), 8.85 (d, J=2.3 Hz, 1H), 7.72 (d, J=2.0 Hz, 1H), 7.48 (dd, J=5.5, 7.8 Hz, 2H), 7.12 (t, J=8.6 Hz, 2H), 5.22 (s, 2H), 4.48 (q, J=7.3 Hz, 2H), 1.46 (t, J=7.0 Hz, 3H). [M+H]=327.2

후처리

  1. customThe crude reaction mixture
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic fractions were washed with brine
  4. concentrationconcentrated under reduced pressure onto silica
  5. customPurification (FCC, SiO2, 0-60%, EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-0f9b0438488c4c24827b9953cac86f6a
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102674B2

반응 노트

불러오는 중…