Pyridine → N-phenylcyclopropanecarboxamide

HRID 479810Notes

Reaction equation

HRID 479810 reaction equation
N1C=CC=CC=1.C(N1CCCOC(C[NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)C1)C1C=CC=CC=1.[CH:29]1([C:32](Cl)=[O:33])[CH2:31][CH2:30]1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:23]1([NH:22][C:32]([CH:29]2[CH2:31][CH2:30]2)=[O:33])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 77637Cyclopropanecarbonyl chlorideHCID 516892Sodium BicarbonateHCID 21904409(4-Benzyl-1,4-oxazepan-2-ylmethyl)-phenyl amine

Product 1

HCID 528617N-phenylcyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Pyridine (3.64 mL, 45.0 mmol) was added to a solution of crude amine 80 (30.0 mmol) in CH2Cl2. The solution was cooled to 0° C. in an ice bath, then cyclopropyl carbonyl chloride (2.99 mL, 33.0 mmol) was added dropwise. The reaction was allowed to warm slowly to room temperature and stirred until the reaction was judged complete by TLC (3.25 h). CH2Cl2 and saturated NaHCO3 were added. The organic layer was removed and the aqueous layer extracted with CH2Cl2 (2×). The organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The resulting oily residue was purified by alumina gel chromatography (96:2:2::Hexanes:CH2Cl2:2N NH3 in EtOH) to obtain 4-benzyl-1,4-ozazepan-2-ylmethyl)-N-phenylcyclopropanamide (85) as a pale yellow oil. 1H NMR (CD3OD) 7.46-7.24 (8H, m), 7.13 (2H, broad d, J=7.2 Hz), 3.90-3.42 (5H, m), 2.92-2.76 (2H, m), 2.62-2.51 (1H, m), 2.30 (1H, dd, 13.7, 8.5 Hz), 1.40-1.20 (2H, m), 0.96-0.82 (3H, m), 0.61 (2H, dd, J=7.9, 2.8 Hz) ppm. 13C NMR (CD3OD) 175.84, 144.04, 140.20, 130.82, 130.54, 129.55, 129.08, 128.43, 77.04, 68.00, 63.63, 59.72, 55.83, 52.94, 31.28, 13.76, 9.34, 9.07 ppm. LRMS: 364.57.

Workup

  1. temperatureto warm slowly to room temperature
  2. customwas judged complete by TLC (3.25 h)
  3. customThe organic layer was removed
  4. extractionthe aqueous layer extracted with CH2Cl2 (2×)
  5. dry with materialThe organic extracts were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting oily residue was purified by alumina gel chromatography (96:2:2::Hexanes:CH2Cl2:2N NH3 in EtOH)

Sources & evidence

ORD record
ord-c233adc954aa417197a2423344184c5c
Source dataset
uspto-grants-2003_11
Patent number
US06645980B1

Reaction notes

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