Acetic Acid → 3-Amino-3-methyl-n-benzylazetidine

HRID 2060940Notes

Reaction equation

HRID 2060940 reaction equation
[CH3:1][C:2]1([N+:13]([O-])=O)[CH2:5][N:4]([CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:3]1.C(O)(=O)C.ClCCl>C(OCC)(=O)C.[Fe]>[NH2:13][C:2]1([CH3:1])[CH2:5][N:4]([CH2:6][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:3]1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 593935783-methyl-3-nitro-N-benzylazetidine2×

Product 1

HCID 593936083-Amino-3-methyl-n-benzylazetidine

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-methyl-3-nitro-N-benzylazetidine [the product of step 2] (3.9 g, 18.9 mmol) in ethyl acetate (370 ml) and 5% acetic acid (370 ml) is heated to reflux. Iron powder (5.25 g, 94.1 mmol) is added portion-wise every 5 minutes. After the addition is complete the reaction mixture is heated at reflux for 6 hours. The cooled reaction mixture is filtered through Hyflo, and the residue washed with ethyl acetate. The filtrate is transferred to a separating funnel and the organic layer separated and discarded. The aqueous layer is treated with 30% NaOH solution with ice cooling to give a pH of ca. 11. Dichloromethane is then added and the mixture vigorously stirred at ambient temperature for 10 minutes. This mixture is filtered through Hyfol, the filtrate transferred to a separating funnel and the organic layer is separated, dried (Na2SO4), filtered, and concentrated. The crude oily product (2.30 g, 69%) is used in the next step without further purification. 1H-NMR (CDCl3): 7.2 (m, 5H), 3.62 (s, 2H), 3.27 (d, 2H), 2.88 (d, 2H), 1.68 (bs, 2H), 1.4 (s, 3H).

Workup

  1. additionAfter the addition
  2. temperatureis heated
  3. temperatureat reflux for 6 hours
  4. customThe cooled reaction mixture
  5. filtrationis filtered through Hyflo
  6. washthe residue washed with ethyl acetate
  7. customThe filtrate is transferred to a separating funnel
  8. customthe organic layer separated
  9. additionThe aqueous layer is treated with 30% NaOH solution with ice cooling
  10. customto give a pH of ca. 11
  11. filtrationThis mixture is filtered through Hyfol
  12. customthe filtrate transferred to a separating funnel
  13. customthe organic layer is separated
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe crude oily product (2.30 g, 69%) is used in the next step without further purification

Sources & evidence

ORD record
ord-ec0189933ff74f57b3b40fd4716137ea
Source dataset
uspto-grants-2012_10
Patent number
US08278464B2

Reaction notes

Loading…