Ammonium Chloride → cis-3-Benzyl-6-bromo-1,2,3,4,4a,9a-hexahydro-3-aza-fluoren-9-one

HRID 1714132Notes

Reaction equation

HRID 1714132 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16]C)=O)[CH:10]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([Br:24])[CH:19]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH4+].[Cl-]>O>[CH2:1]([N:8]1[CH2:9][C@H:10]2[C@H:11]([C:14](=[O:16])[C:23]3[C:18]2=[CH:19][C:20]([Br:24])=[CH:21][CH:22]=3)[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 25517Ammonium ChlorideHCID 68504079Methyl 1-benzyl-3-(3-bromophenyl)piperidine-4-carboxylate

Product 1

HCID 15953813cis-3-Benzyl-6-bromo-1,2,3,4,4a,9a-hexahydro-3-aza-fluoren-9-oneYield 18.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of methyl 1-benzyl-3-(3-bromophenyl)piperidine-4-carboxylate (3.7 g, 9.5 mmol) and polyphosphoric acid (37 g) was heated at 180° C. for 3 h then cooled to 0.20° C. To the reaction mixture H2O and saturated NH4Cl aqueous solution were added, successively then extracted with CH2Cl2. The combined organic solution was dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed in silica gel column (Hex/EtOAc 9/1) to obtain the title compound (631 mg, 1.8 mmol) MS (ES) 356.1 (M+H) along with the regio-isomer example 2 as the less polar fraction.

Workup

  1. temperaturethen cooled to 0.20° C
  2. extractionsuccessively then extracted with CH2Cl2
  3. dry with materialThe combined organic solution was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed in silica gel column (Hex/EtOAc 9/1)

Sources & evidence

ORD record
ord-d317ab9ee0154d0a830a315c6bb39fb9
Source dataset
uspto-grants-2010_09
Patent number
US07795436B2

Reaction notes

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