Tetrahydrofuran → HCID 178498566, compound

HRID 1600048Notes

Reaction equation

HRID 1600048 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

4

Reactant 3

HCID 8028TetrahydrofuranHCID 24386Thionyl ChlorideHCID 178498606HCID 178498606, compound

Product 1

HCID 178498566HCID 178498566, compound

Conditions

Temperature
0 °C

Procedure

The free base of 4-(trifluoromethoxy)phenyl hydrazine was prepared from thehydrochloride 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 mK). 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). 1H NMR 12.67 (s, 1H, exchangeable), 10.79 (s, 1H, exchangeable), 8.37 (br s, 1H, exchangeable), 8.13 (d, J=8.61 Hz, 1H), 7.83 (d, J=1.76 Hz, 1H), 7.48 (dd, J=8.61, 1.76 Hz, 1H), 7.21 (d, J=8.50 Hz, 2H), 6.94 (d,J=8.50 Hz, 2H), 3.70 (s, 3H).

Workup

  1. customAfter 3 hours the crude acid chloride was isolated

Sources & evidence

ORD record
ord-fc3ac25425eb41b389af815dc8023947
Source dataset
uspto-grants-1998_04
Patent number
US05744471

Reaction notes

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