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

HRID 2063304Notes

Reaction equation

HRID 2063304 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) was 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 trice with ethyl acetate. The combined organic solutions were washed trice with water and then dried by a phase separator column. The solvent was removed by to 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-[(25)-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).

Workup

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

Sources & evidence

ORD record
ord-27a565dc8e3e42c98dcc1852e9886808
Source dataset
uspto-grants-2012_10
Patent number
US08288370B2

Reaction notes

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