Phosphorus oxychloride → HCID 131734344, compound
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[NH:8][CH:7]=[CH:6][C:5]2=O.[Br:14][C:15]1[C:16]([F:26])=[C:17]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[CH:19][C:18]2=O.P(Cl)(Cl)([Cl:29])=O>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][CH:6]=[C:5]2[Cl:29].[Br:14][C:15]1[C:16]([F:26])=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][CH:19]=[C:18]2[Cl:29]Participants
Procedure
A mixture of 6-bromo-7-fluoroquinolin-4(1H)-one/6-bromo-5-fluoroquinolin-4(1H)-one (37.6 g, 155 mmol) and phosphorus oxychloride (101 ml, 1087 mmol) was stirred at RT overnight. The POCl3 was removed via rotovap and the resulting material was dissolved into DCM. This mixture was quenched (very carefully) via pipette addition of sat. aq. Na2CO3. Once the mixture was neutralized, the layers were separated. The aqueous layer was further extracted with DCM. The combined organic layers were concentrated. The resulting material was taken into EtOAc and passed through a short plug of silica gel and concentrated to yield 6-bromo-4-chloro-7-fluoroquinoline/6-bromo-4-chloro-5-fluoroquinoline (40.42 g, 100%) of a brown solid that was a mixture of regioisomers (31:69, by LCMS). MS: m/z: 260.0/262.0 [M+H]+.
Workup
- customThe POCl3 was removed via rotovap
- dissolutionthe resulting material was dissolved into DCM
- customThis mixture was quenched (very carefully)
- additionvia pipette addition of sat. aq. Na2CO3
- customthe layers were separated
- extractionThe aqueous layer was further extracted with DCM
- concentrationThe combined organic layers were concentrated
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-0a4d510eeb844fcca03a430285f36365
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09216965B2
Reaction notes
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