Methanesulfonic Acid → ethyl 2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxylate

HRID 595556노트

반응식

HRID 595556 반응식
[Cl:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[F:17])[NH:9]2)[C:5]([OH:18])=[CH:4][CH:3]=1.[CH2:19]([O:21][C:22](=[O:25])[CH:23]=O)[CH3:20].S(O)(C)(=O)=O>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:23]([C:22]([O:21][CH2:19][CH3:20])=[O:25])[N:9]3[C:10]4[CH:11]=[CH:12][CH:13]=[C:14]([F:17])[C:15]=4[CH2:16][CH:8]3[C:6]=2[N:7]=1

참가 물질

6

반응물 3

HCID 6395Methanesulfonic AcidHCID 70211Ethyl oxoacetateHCID 867262936-Chloro-2-(4-fluoroindolin-2-yl)pyridin-3-ol

생성물 1

HCID 86728252ethyl 2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxylate수율 90.5%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
50 °C

실험 절차

To a solution of 6-chloro-2-(4-fluoroindolin-2-yl)pyridin-3-ol (8.53 g, 32.31 mmol) and glyoxylic acid ethyl ester (6.59 g, 64.59 mmol) in THF (80 mL), MsOH (0.31 g, 3.23 mmol) was added. The mixture was stirred at 50° C. for 2 hours. The mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated. The residue was purified by column chromatography (PE: EtOAc=10:1) to afford ethyl 2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxylate (10.2 g, yield: 90.3%). 1H-NMR (CDCl3, 400 MHz) δ 7.04˜7.13 (m, 3H), 6.63 (d, J=8.0 Hz, 1H), 6.55 (t, J=8.4 Hz, 1H), 6.03 (s, 1H), 5.09 (d, J=8.8 Hz, 1H), 4.22˜4.34 (m, 2H), 3.73 (d, J=16.4 Hz, 1H), 3.44˜3.51 (m, 1H), 1.29 (d, J=7.2 Hz, 3H). MS (M+H)+: 349.

후처리

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine (30 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (PE: EtOAc=10:1)

출처 및 근거

ORD 기록
ord-f5572df3bb61454985113dfdc3449c84
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242998B2

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