Diisopropylethylamine → 3-bromo-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5-(trifluoromethyl)benzamide

HRID 426081Notes

Reaction equation

HRID 426081 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:12][CH:13]=[CH2:14])[CH2:9][NH:10][CH3:11])=[CH:4][CH:3]=1.[Br:15][C:16]1[CH:17]=[C:18]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[C:19]([OH:21])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:15][C:16]1[CH:17]=[C:18]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[C:19]([N:10]([CH2:9][C@H:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[CH2:12][CH:13]=[CH2:14])[CH3:11])=[O:21]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 110867883-Bromo-5-(trifluoromethyl)benzoic acidHCID 15536023[(2S)-2-(4-Fluorophenyl)pent-4-en-1-yl]methylamine

Product 1

HCID 161193783-bromo-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5-(trifluoromethyl)benzamideYield 69.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]methylamine (see Bioorg. Med. Chem. Lett; 2001; 265-270; 0.54 g, 2.8 mmol) and 3-bromo-5-trifluoromethyl benzoic acid (0.81 g, 3.0 mmol) in DMF (7 mL) were added TBTU (0.96 g, 3.0 mmol) and DIPEA (1.41 g, 10.9 mmol). The reaction mixture was stirred under nitrogen overnight at RT and then partitioned between ethyl acetate and an aqueous NaHCO3 solution. The aqueous phase was extracted twice with ethyl acetate. The combined organic solutions were washed twice with water and then dried by a phase separator column. The solvent was removed by evaporation and the product was purified by chromatography on silica gel (ethyl acetate-heptane 10% to 17%). There was obtained 0.86 g (68%) of 3-bromo-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5-(trifluoromethyl)benzamide. 1H NMR (500 MHz, CDCl3): 2.1-3.8 (cm, 8H), 4.9-5.1 (m, 2H), 5.5-5.8 (m, 1H), 6.8-7.4 (cm, 6H), 7.8 (s, 1H). LCMS: m/z 445 (M+1)+.

Workup

  1. custompartitioned between ethyl acetate
  2. extractionThe aqueous phase was extracted twice with ethyl acetate
  3. washThe combined organic solutions were washed twice with water
  4. customdried by a phase separator column
  5. customThe solvent was removed by evaporation
  6. customthe product was purified by chromatography on silica gel (ethyl acetate-heptane 10% to 17%)

Sources & evidence

ORD record
ord-580beba2567b43cc91cbe11e8a46576b
Source dataset
uspto-grants-2012_01
Patent number
US08106208B2

Reaction notes

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