Phosphorus oxychloride → 7-(Benzyloxy)-4-chloro-6-methoxyquinoline
Reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](O)=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:24]>>[Cl:24][C:13]1[C:12]2[C:17](=[CH:18][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[C:10]([O:20][CH3:21])[CH:11]=2)[N:16]=[CH:15][CH:14]=1Participants
Procedure
7-Benzyloxy-6-methoxy-quinolin-4-ol (WO2006108059) (1 g) was refluxed with POCl3 (8 ml) for 3 hours. The reaction was evaporated and dissolved into DCM (80 ml) that was washed with ice water followed by brine. The organic layer was dried with Na2SO4 and evaporated to dryness to give a dark yellow solid as 4-chloro-7-benzyloxy-6-methoxy-quinoline that was mixed with 6-Hydroxy-N-methyl-1-naphthamide (600 mg), DMAP (1.5 eq) in dioxane (40 ml). The reaction was refluxed for three days and diluted with EtOAc, water and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried. The solution was evaporated and purified with silica gel column to give 6-(7-(benzyloxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (210 mg). This product was mixed with Pd/C (120 mg, 10%), HCONH4 (210 mg) in EtOH (20 ml). The mixture was refluxed for 1 hour and evaporated then mixed with water (2 ml). The solid was filtered and washed with water twice and cold MeOH as 6-(7-hydroxy-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide for next step without further purification.
Workup
- customThe reaction was evaporated
- dissolutiondissolved into DCM (80 ml) that
- washwas washed with ice water
- dry with materialThe organic layer was dried with Na2SO4
- customevaporated to dryness
Sources & evidence
- ORD record
- ord-a085f707daf04767bc168537daaed222
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08513283B2
Reaction notes
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