Tetrahydrofuran → HCID 178498566, compound
Reaction equation
O1CCCC1.[C:6]([C:10]1[C:11]([C:22]([OH:24])=O)=[N:12][C:13]2[C:18]([C:19]=1[OH:20])=[CH:17][CH:16]=[C:15]([Cl:21])[CH:14]=2)([O:8][CH3:9])=[O:7].S(Cl)([Cl:27])=O>>[C:6]([C:10]1[C:11]([C:22]([Cl:27])=[O:24])=[N:12][C:13]2[C:18]([C:19]=1[OH:20])=[CH:17][CH:16]=[C:15]([Cl:21])[CH:14]=2)([O:8][CH3:9])=[O:7]Participants
Conditions
- Temperature
- 0 °C
Procedure
The free base of 4-(trifluoromethoxy)phenyl hydrazine was prepared from the hydrochloride salt by treatment of the suspended salt (400 mg, 1.75 mM) in ethyl acetate (50 mL) with 2N sodium hydroxide(50 mL). The organic layer was separated, dried over magnesium sulfate and concentrated in vacuo to provide the free base of 4-(trifluoromethoxy)phenyl hydrazine (325 mg, 1.69 mM). This material was placed into anhydrous tetrahydrofuran (5 mL) and cooled to 0° C. under a nitrogen atmosphere. Concurrently, 3-carbomethoxy-7-chloro-4-hydroxyquinoline-2-carbonyl chloride was prepared from 3-carbomethoxy-7-chloro-4-hydroxyquinoline-2-carboxylic acid (121 mg, 0.43 mM) by heating to 60° C. in thionyl chloride (4 mL). After 3 hours the crude acid chloride was isolated by distilling away the excess thionyl chloride. The crude3-carbomethoxy-7-chloro-4-hydroxyquinoline-2-carbonyl chloride (130 mg, 0.43 mM) was then placed in anhydrous tetrahydrofuran (3 mL) at ambient temperature and added via cannula to the 4-(trifluoromethoxy)phenyl hydrazine solution. After 30 minutes the reaction mixture was poured into 1.0N hydrochloric acid producing a precipitate. The solid was isolated to yield the title compound (185 mg, 95%) as an off-white solid, mp 346-350° C.; MS 456 (M+H).
Workup
- customAfter 3 hours the crude acid chloride was isolated
Sources & evidence
- ORD record
- ord-39b74bd37f284d87bdaeaaa1e28ddb62
- Source dataset
- uspto-grants-2001_05
- Patent number
- US06232313B1
Reaction notes
Loading…