Diphenylmethane → N-(Cyclopropylmethyl)-3-[4-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide

HRID 2081397Notes

Reaction equation

HRID 2081397 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11]N=C1)([N:3]1[CH:7]=[CH:6]N=[CH:4]1)=[O:2].Cl.N[CH2:15][CH2:16]C1CC1.C(N(CC)CC)C.[F:27][C:28]([F:41])([F:40])[C:29]1[CH:39]=[CH:38][C:32]([O:33]C2CNC2)=[CH:31][CH:30]=1.C1(CC2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl.O>[CH:11]1([CH2:12][NH:8][C:1]([N:3]2[CH2:4][CH:6]([O:33][C:32]3[CH:38]=[CH:39][C:29]([C:28]([F:27])([F:40])[F:41])=[CH:30][CH:31]=3)[CH2:7]2)=[O:2])[CH2:16][CH2:15]1

Participants

8

Reactant 5

HCID 7580DiphenylmethaneHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 128124993-[4-(Trifluoromethyl)phenoxy]azetidineHCID 219160802-Cyclopropylethanamine hydrochloride

Product 1

HCID 15053424N-(Cyclopropylmethyl)-3-[4-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred mixture of 4.4 g (0.027 mole) of 1,1'-carbonyldiimidazole and 2.9 g (0.027 mole) of (aminoethyl) cyclopropane hydrochloride in 50 ml of methylene chloride was treated with the dropwise addition of 2.73 g (0.027 mole) of triethylamine. The reaction was exothermic. The mixture was cooled while stirring for 1 hr, then 9.6 g (0.025 mole) of 3-[4-(trifluoromethyl)phenoxy]azetidine, 56.66% purity, (contains diphenylmethane) was added all at once and stirring continued for 18 hr. The reaction mixture was concentrated on a rotary evaporator to give an amber residue. Trituration of this residue with 30/60 petroleum ether gave only an insoluble oil. The trituration step was repeated with 2×20 ml of 30/60 petroleum ether and the residue treated with water to yield a white solid. The solid was recrystallized from isopropyl ether to yield 4.8 g (61.8%) of white platelike crystals; after during at 80° C. under 0.5 mm Hg vacuum, m.p. 132°-133° C.

Workup

  1. temperatureThe mixture was cooled
  2. stirringstirring
  3. waitcontinued for 18 hr
  4. concentrationThe reaction mixture was concentrated on a rotary evaporator
  5. customto give an amber residue
  6. customto yield a white solid
  7. customThe solid was recrystallized from isopropyl ether
  8. customto yield 4.8 g (61.8%) of white platelike crystals
  9. customduring at 80° C.

Sources & evidence

ORD record
ord-b16551c4637f4bc8b69a45bc19b8cc19
Source dataset
uspto-grants-1993_02
Patent number
US05183902

Reaction notes

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