Reaction #41802

Reaction equation

water

NaOH

water

t-butyl ester

2-Fluoro-3-(4-methyl-piperazin-1-yl)-6-nitro-phenylamine

LAH

→

2

3-Fluoro-4-(4-methyl-piperazin-1-yl)-benzene-1,2-diamine

Solvents

THF

THF

Conditions

Workup

1. 1
   OtherA flame dried 500 mL three-necked round bottom flask
2. 2
   Otherpurged with N2
3. 3
   workup.ADDITIONwas slowly added
4. 4
   Otherunder 5° C
5. 5
   workup.WAITat rt for 30 min
6. 6
   FiltrationThe resulting suspension was filtered through Celite
7. 7
   Washwashed with ethyl acetate and methanol
8. 8
   OtherThe crude product was absorbed onto silica gel
9. 9
   Otherpurified by flash chromatography (97:3 CH2Cl2/MeOH)

Procedure

A flame dried 500 mL three-necked round bottom flask purged with N2 was charged with LAH (2.32 g, 58.0 mmol) and dry THF (60 mL). The resulting suspension was cooled to 0° C. and a suspension of t-butyl ester 1 (10.0 g, 29.0 mmol) in dry THF (60 mL) was slowly added while keeping the internal reaction temperature under 5° C. The reaction was stirred at 0° C. for 30 min then at rt for 30 min. After the reaction was judged complete, the mixture was treated with successive dropwise addition of water (2.3 mL), 10% NaOH (2.3 mL), and water (7.2 mL). The resulting suspension was filtered through Celite, washed with ethyl acetate and methanol, and the collected organics concentrated. The crude product was absorbed onto silica gel and purified by flash chromatography (97:3 CH2Cl2/MeOH) to give 2 as an orange solid: 1H NMR (300 MHz, CDCl3) δ 8.40 (d, J=5.5 Hz, 1H), 8.05 (br s, 1H), 7.96 (d, J=2.75 Hz, 1H), 7.29 (d, J=2.75 Hz, 1H), 6.92 (d, J=9.35 Hz, 1H), 6.75 (m, 2H), 4.68 (s, 2H), 3.07 (d, J=5.23 Hz, 3H).

Source