Diisopropylethylamine → 3-Fluoro-5-trifluoromethylbenzyl 3-oxo-1-isopropylpentane-carboxamide

HRID 1725760Notes

Reaction equation

HRID 1725760 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)[CH2:5]N.C([N:17](C(C)C)CC)(C)C.[CH:23]([C:26]1([C:32](Cl)=[O:33])[CH2:30][CH2:29][C:28](=[O:31])[CH2:27]1)([CH3:25])[CH3:24]>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)[CH2:5][C:26]([CH:23]([CH3:25])[CH3:24])([C:32]([NH2:17])=[O:33])[CH2:27][C:28](=[O:31])[CH2:29][CH3:30]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27333043-Fluoro-5-(trifluoromethyl)benzylamineHCID 186143461-Isopropyl-3-oxocyclopentanoyl chloride

Product 1

HCID 867608163-Fluoro-5-trifluoromethylbenzyl 3-oxo-1-isopropylpentane-carboxamideYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-fluoro-5-trifluoromethylbenzylamine (3.07 g, 15.9 mmol) and diisopropylethylamine (2.77 mL, 15.9 mmol) in dichloromethane (60 mL) was slowly treated with 1-isopropyl-3-oxocyclopentanoyl chloride (3.0 g, 15.9 mmol) and stirred at ambient temperature overnight. The mixture was diluted with dichloromethane washed with a saturated solution of sodium bicarbonate, 2N HCl, water and brine. The organic phase was dried with anhydrous magnesium sulfate and the solvent was evaporated in vacuo to yield 6.0 g of crude product. This was further purified by column chromatography (silica gel, ethyl acetate hexane (40:60%) to yield 4.10 g (85%) of the pure product. 1H NMR (500 MHz, CDCl3): 7.32 (s, 1H), 7.23 (d, J=8.23 Hz, 1H), 7.19 (d, J=8.93 Hz, 1H), 4.52 (m, 2H), 2.79 (d, J=18.53 Hz, 1H), 2.40 to 2.18 (bm, 4H), 2.0 (m, 2H), 0.98 (d, J=6.63 Hz, 3H), 0.96 (d, 6.60 Hz, 3H).

Workup

  1. washwashed with a saturated solution of sodium bicarbonate, 2N HCl, water and brine
  2. dry with materialThe organic phase was dried with anhydrous magnesium sulfate
  3. customthe solvent was evaporated in vacuo
  4. customto yield 6.0 g of crude product
  5. customThis was further purified by column chromatography (silica gel, ethyl acetate hexane (40:60%)

Sources & evidence

ORD record
ord-9f09b93ea2a74434a830d23ac7d2666a
Source dataset
uspto-grants-2009_02
Patent number
US07491737B2

Reaction notes

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