Triethylamine → 2,5-Difluoro-3-fluoromethyl-4-(4-ethoxycarbonyl-1-piperazinyl)nitrobenzene

HRID 1638671Notes

Reaction equation

[F:1][C:2]1[C:3]([N:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][CH2:15]2)=[C:4]([C:7]([F:13])=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1)[CH2:5]O.C(N(S(F)(F)[F:31])CC)C.C(N(CC)CC)C>ClCCl>[F:13][C:7]1[C:4]([CH2:5][F:31])=[C:3]([N:14]2[CH2:15][CH2:16][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:18][CH2:19]2)[C:2]([F:1])=[CH:9][C:8]=1[N+:10]([O-:12])=[O:11]

Participants

Conditions

Temperature: 0 °C

Procedure

3,6-Difluoro-2-(4-ethoxycarbonyl-1-piperazinyl)-5-nitrobenzyl alcohol (1.5 g) is dissolved in dichloromethane (18 ml), and thereto is added dropwise a solution of diethylaminosulfur trifluoride (DAST) (0.7 ml) and triethylamine (0.78 ml) in dichloromethane (3 ml) over a period of 5 minutes while stirring at 0° C. in ice bath. The mixture is stirred at 0° C. for 1.2 hour, and thereto is further added DAST (0.3 ml). After 5 minutes, the reaction mixture is poured into ice water, and the organic layer is separated. The solvent is distilled off under reduced pressure, and the residue is purified by silica gel column chromatography (solvent, ethyl acetate:n-hexane=1:10→1:5 v/v) to give 2,5-difluoro-3-fluoromethyl-4-(4-ethoxycarbonyl-1-piperazinyl)nitrobenzene (1.1 g).

Workup

stirringThe mixture is stirred at 0° C. for 1.2 hour
customthe organic layer is separated
distillationThe solvent is distilled off under reduced pressure
customthe residue is purified by silica gel column chromatography (solvent, ethyl acetate:n-hexane=1:10→1:5 v/v)

Sources & evidence

ORD record: ord-dce3ba3ec6164bcca9fa17e3c8008928
Source dataset: uspto-grants-1989_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04880806

Reaction notes

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