Triethylamine → N-[cis-2-(4-chlorophenyl)cyclobutyl]-2-(trifluoromethyl)benzamide

HRID 1482440Notes

Reaction equation

HRID 1482440 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:11][CH2:10][CH:9]2[NH2:12])=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=1[C:24](Cl)=[O:25]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]2[CH2:11][CH2:10][C@H:9]2[NH:12][C:24](=[O:25])[C:23]2[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=2[C:21]([F:20])([F:31])[F:32])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 675612-(Trifluoromethyl)benzoyl chlorideHCID 810131342-(4-Chlorophenyl)cyclobutanamine

Product 1

HCID 71765835N-[cis-2-(4-chlorophenyl)cyclobutyl]-2-(trifluoromethyl)benzamideYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4-chlorophenyl)cyclobutanamine (105 mg, 0.55 mmol) and triethylamine (140 mg 2.5 eq.) in THF was added 2-trifluoromethyl-benzoylchloride (127.46 mg, 1.1 eq.) at 0° C. The RM was stirred at rt for 2 h. Et3N.HCl was filtered off and the THF was evaporated. The residue—mixture of two isomers cis and trans (2:1) was purified and separated with chromatography on silica gel, eluent i-Hx:diethylether 1:1, (KMnO4 stain). N-[cis-2-(4-chlorophenyl)cyclobutyl]-2-(trifluoromethyl)benzamide (cis) (33 mg, m.p. 147-9° C.) and its trans isomer (17 mg, m.p. 117-9° C.) were isolated as crystalline products.

Workup

  1. filtrationEt3N.HCl was filtered off
  2. customthe THF was evaporated
  3. additionThe residue—mixture of two isomers
  4. customtrans (2:1) was purified
  5. customseparated with chromatography on silica gel, eluent i-Hx

Sources & evidence

ORD record
ord-e7bed3d0169f453787b0fcfdba8be5d4
Source dataset
uspto-grants-2016_08
Patent number
US09414589B2

Reaction notes

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