Benzene, 4-chloro-1-methyl-2-nitro- → 6-Chloroindole

Temperature

100 °C

A mixture of 4-chloro-2-nitrotoluene (34 g, 0.2 mole), dimethylformamide dimethyl acetal (28 mL, 0.2 mole) and pyrrolidine (25 mL 0.3 mole) in dimethylformamide (DMF) is heated at 100° C. for 72 h, cooled to room temperature and concentrated in vacuo to give a deep red residue. The residue is taken up in methanol/tetrahydro-furan (1:1), treated with about 2 mL of a Raney nickel slurry and hydrogenated at atmospheric pressure. The reaction is monitored by GC, TLC and H2 uptake. After 2 hours, the hydrogenation is continued at 20 psi-40 psi for a total hydrogenation time of 24 hours. The resultant reaction mixture is filtered through diatomaceous earth. The filtercake is washed with methylene chloride and the combined filtrate is washed sequentially with 1 N HCl and saturated NaHCO3, dried over MgSO4 and concentrated in vacuo to give a brown oil residue. The residue is crystallized in hexanes to give the title product as a brown solid, 22 g (72.6 % yield), identified by IR, 1HNMR, 13CNMR and mass spectral analyses.

1. temperaturecooled to room temperature
2. concentrationconcentrated in vacuo
3. customto give a deep red residue
4. customis continued at 20 psi-40 psi for a total hydrogenation time of 24 hours
5. customThe resultant reaction mixture
6. filtrationis filtered through diatomaceous earth
7. washThe filtercake is washed with methylene chloride
8. washthe combined filtrate is washed sequentially with 1 N HCl and saturated NaHCO3
9. dry with materialdried over MgSO4
10. concentrationconcentrated in vacuo
11. customto give a brown oil residue
12. customThe residue is crystallized in hexanes

ORD record

ord-e9f87ccd25994d0d93953b1a57d957ae

Source dataset

uspto-grants-1997_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05599832