Ethyl Acetate → 5-Fluoro-2-{[(2E)-3-phenylprop-2-enyl]oxy}aniline

HRID 1867261Notes

Reaction equation

[C:1]1(/[CH:7]=[CH:8]/[CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[N+:18]([O-])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH4+].[Cl-].CCOC(C)=O>CO.[Zn]>[F:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][CH2:9]/[CH:8]=[CH:7]/[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[C:12]([CH:13]=1)[NH2:18]

Participants

Conditions

Temperature: 25 °C

Procedure

4-Fluoro-2-nitrophenyl (2E)-3-phenylprop-2-enyl ether (5-1, 20.2 g, 73.9 mmol) was dissolved in MeOH (300 mL) and treated with NH4Cl (20.5 g, 370 mmol) and Zn powder (24.2 g, 370 mmol) in small portions to prevent temperature from exceeding 50° C. during the addition. The suspension was vigorously stirred at 25° C. and then at 60° C. until completion as monitored by TLC and LC/MS. Upon completion, EtOAc was added (900 mL) and the reaction was filtered through celite and concentrated. The product was recrystallized from EtOAc/hexanes after a filtration to remove insoluble NH4Cl, and pure 5-fluoro-2-{[(2E)-3-phenylprop-2-enyl]oxy}aniline (5-2) was isolated as a brown solid. 1H NMR (300 MHz, CDCl3) δ 7.38 (m, 5H), 6.74 (dd, J=8.8, 4.9 Hz, 1H), 6.72 (d, J=17.4 Hz, 1H), 6.47 (dd, J=9.7, 3.1 Hz, 1H), 6.42 (m, 2H), 4.67 (dd, J=5.9, 1.3 Hz, 2H), 3.22 (br s, 2H); MS (M+H+, C15H14FNO) 244.2 found 244.3 required.

Workup

additionfrom exceeding 50° C. during the addition
customat 60° C.
filtrationthe reaction was filtered through celite
concentrationconcentrated
customThe product was recrystallized from EtOAc/hexanes
filtrationafter a filtration
customto remove insoluble NH4Cl

Sources & evidence

ORD record: ord-75b43e3a7bbb4c77af187ce1d991c8dd
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07632833B2

Reaction notes

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