Hydrochloric Acid → 3-Fluoro-5-(1-methyl-piperidin-4-yloxy)-phenylamine

HRID 1821995Notes

Reaction equation

HRID 1821995 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:13]=[C:14]([N+:16]([O-])=O)[CH:15]=1)[O:5][CH:6]1[CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]1.Cl>[Fe].CO>[F:1][C:2]1[CH:15]=[C:14]([NH2:16])[CH:13]=[C:4]([O:5][CH:6]2[CH2:7][CH2:8][N:9]([CH3:12])[CH2:10][CH2:11]2)[CH:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 578937804-(3-Fluoro-5-nitro-phenoxy)-1-methyl-piperidine

Product 1

HCID 578936363-Fluoro-5-(1-methyl-piperidin-4-yloxy)-phenylamineYield 56%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 887MethanolSolvent

Procedure

Combine 4-(3-fluoro-5-nitro-phenoxy)-1-methyl-piperidine (preparation 16, 2.75 g, 10.82 mmol), iron dust (2.0 g, 35.69 mmol), methanol (150 mL) and 1M aqueous hydrochloric acid solution (3.25 mL, 3.25 mmol), stir and heat at reflux. After 32 hr., cool to ambient temperature, filter through celite and concentrate to an oil. Partition between ethyl acetate (100 mL) and 1M aqueous sodium hydroxide solution (50 mL), separate the organic layer, dry over sodium sulfate, filter and concentrate. Purify residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride to give the title compound (1.35 g, 56%). 1H NMR (CDCl3): 6.0 (m, 3H), 4.2 (m, 1H), 3.7 (bs, 2H), 2.7 (m, 2H), 2.3 (m, 5H), 2.0 (m, 2H), 1.8 (m, 2H).

Workup

  1. temperatureheat
  2. temperatureat reflux
  3. filtrationfilter through celite
  4. concentrationconcentrate to an oil
  5. customPartition between ethyl acetate (100 mL) and 1M aqueous sodium hydroxide solution (50 mL)
  6. customseparate the organic layer
  7. dry with materialdry over sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate
  10. washPurify residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride

Sources & evidence

ORD record
ord-c315c441af2a4c7b8e988cdc1380952f
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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