2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → ethyl 2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxylate

HRID 595557Notes

Reaction equation

HRID 595557 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH2:15][CH:7]3[C:6]=2[N:24]=1.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>C1(C)C=CC=CC=1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH:15]=[C:7]3[C:6]=2[N:24]=1

Participants

5

Reactant 2

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 86728252ethyl 2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxylate

Product 1

HCID 86728253ethyl 2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole-6-carboxylateYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of ethyl 2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxylate (10.22 g, 29.36 mmol) and DDQ (8.67 g, 38.17 mmol) in toluene (80 mL) was stirred at 80° C. for 2 hours. The mixture was then diluted with water (50 mL) and extracted with EtOAc (30 mL*3). The organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated. The residue was purified by column chromatography (PE:EtOAc=20:1) to afford ethyl 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxylate (8.64 g, yield: 85%), which was also prepared from 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol and methyl 2,2-dibromoacetate in the presence of base, such as DBU etc. 1H-NMR (CDCl3, 400 MHz) δ 7.33 (d, J=8.4 Hz, 1H), 7.30 (s, 1H), 7.09˜7.18 (m, 3H), 6.78˜6.83 (m, 1H), 6.52 (s, 1H), 3.96˜4.09 (m, 2H), 1.02 (t, J=7.2 Hz, 3H). MS (M+H)+: 347.

Workup

  1. extractionextracted with EtOAc (30 mL*3)
  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=20:1)

Sources & evidence

ORD record
ord-c4096c99cfd64f47aaa7a5dacdce4c8c
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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