Pyridine → N-phenylcyclopropanecarboxamide

HRID 988784Notes

Reaction equation

HRID 988784 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-01403d62c62d4b728d51aca17fc59278
Source dataset
uspto-grants-2003_10
Patent number
US06635661B2

Reaction notes

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