3-(Trifluoromethyl)aniline → 3-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-N-(3-trifluoromethyl-phenyl)-benzamide

HRID 1853958

Reaction equation

HRID 1853958 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([NH2:9])[CH:6]=[CH:7][CH:8]=1.[O:12]1[C:16]2([CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=3[CH3:31])[C:25](O)=[O:26])[CH2:18][CH2:17]2)[O:15][CH2:14][CH2:13]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[O:15]1[C:16]2([CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=3[CH3:31])[C:25]([NH:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=3)=[O:26])[CH2:18][CH2:17]2)[O:12][CH2:13][CH2:14]1

Participants

7

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673566093-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-benzoic acid

Product 1

HCID 673547213-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-N-(3-trifluoromethyl-phenyl)-benzamideYield 68.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-Trifluoromethyl-phenylamine (24.1 mg, 0.15 mmol), 3-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-benzoic acid [as prepared in reference 3] (41.5 mg, 0.15, and DIPEA (78 μl, 0.45 mmol) in DMF was added HATU (59 mg, 0.15 mmol), and the reaction mixture was stirred for 3 hour at room temperature. The reaction mixture was diluted with ethyl acetate and washed with 5% aqueous sodium bisulphate solution, saturated aqueous sodium bicarbonate solution and brine. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product obtained was purified by column chromatography (SiO2, 2-10% methanol in chloroform) to give 43.1 mg (68.6%) of 3-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-4-methyl-N-(3-trifluoromethyl-phenyl)-benzamide [25] as a pale yellow solid.

Workup

  1. washwashed with 5% aqueous sodium bisulphate solution, saturated aqueous sodium bicarbonate solution and brine
  2. dry with materialThe organic layer was dried over sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product obtained
  5. customwas purified by column chromatography (SiO2, 2-10% methanol in chloroform)

Sources & evidence

ORD record
ord-a3b143116da04932b61cfdf08ad4daba
Source dataset
uspto-grants-2015_02
Patent number
US08962637B2

Linked notes

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