Ammonia → 2-amino-1-(4-chloro-phenyl)-3-cyclopentyl-propan-1-one O-methyl-oxime

HRID 719126Notes

Reaction equation

HRID 719126 reaction equation
[CH3:1][O:2][N:3]=[C:4]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[CH:5](Br)[CH2:6][CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1.[NH3:20]>CO>[CH3:1][O:2][N:3]=[C:4]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[CH:5]([NH2:20])[CH2:6][CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 738525452-bromo-1-(4-chloro-phenyl)-3-cyclopentyl-propan-1-one O-methyl-oxime

Product 1

HCID 738525462-amino-1-(4-chloro-phenyl)-3-cyclopentyl-propan-1-one O-methyl-oximeYield 45%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

The 2-bromo-1-(4-chloro-phenyl)-3-cyclopentyl-propan-1-one O-methyl-oxime (1.16 g, 2.901 mmol) was dissolved in a solution of ammonia in methanol (30 mL, ˜7 N). The reaction flask was sealed with a Teflon stopper, and the reaction mixture was stirred at 55–60° C. for 2 d. It was cooled to 0° C. then the stopper was removed. The reaction mixture was concentrated to remove ammonia and methanol. The residue was partitioned between water and diethyl ether. The product was extracted with diethyl ether (2×20 mL). The organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32–63 μm, 60 Å silica gel) eluting with 50–100% ethyl acetate+0.1% triethylamine in hexanes yielded 2-amino-1-(4-chloro-phenyl)-3-cyclopentyl-propan-1-one O-methyl-oxime (423 mg, 45%) as yellow oil.

Workup

  1. customthe stopper was removed
  2. concentrationThe reaction mixture was concentrated
  3. customto remove ammonia and methanol
  4. customThe residue was partitioned between water and diethyl ether
  5. extractionThe product was extracted with diethyl ether (2×20 mL)
  6. washThe organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32–63 μm, 60 Å silica gel)
  10. washeluting with 50–100% ethyl acetate+0.1% triethylamine in hexanes

Sources & evidence

ORD record
ord-f9c81ba470ec4a70a52f0114d2b356eb
Source dataset
uspto-grants-2006_11
Patent number
US07132421B2

Reaction notes

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