4-Fluorobenzoic Acid → HCID 58235429, compound

HRID 1895917Notes

Reaction equation

HRID 1895917 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([S:9]([N:12]2[CH2:16][CH2:15][C@H:14]([O:17][NH2:18])[CH2:13]2)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[OH:21]N1C2C=CC=CC=2N=N1.[F:31][C:32]1[CH:40]=[CH:39]C(C(O)=O)=[CH:34][CH:33]=1.C(N(CC)[CH:45]([CH3:47])[CH3:46])(C)C>CN(C)C=O>[F:31][C:32]1[CH:40]=[CH:39][C:47]([CH2:45][C:46]([NH:18][O:17][C@H:14]2[CH2:15][CH2:16][N:12]([S:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:19])[F:20])[CH:4]=3)(=[O:11])=[O:10])[CH2:13]2)=[O:21])=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 99734-Fluorobenzoic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67118437HCID 67118437, compound

Product 1

HCID 58235429HCID 58235429, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (68.0 mg, 0.35 mmol) was added to a solution of (S)—O-(1-(3-(trifluoromethyl)phenylsulfonyl)pyrrolidin-3-yl)hydroxylamine (100 mg, 0.32 mmol), 1-hydroxybenzotriazole (45.0 mg, 0.35 mmol), 4-fluorobenzoic acid (45 mg, 0.32 mmol) and N,N-diisopropylethylamine (125 mg, 0.97 mmol) in N,N-dimethylformamide (10 m1). The reaction mixture was stirred at room temperature for 17 hours and quenched with H2O (30 ml). The aqueous phase was extracted with ethyl acetate (30 ml×3) and the combined organic phase was washed with aqueous 0.1 N HCl solution (20 ml), H2O (30 ml×3) and brine (30 ml), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/hexane: 33/67) to give (S)-2-(4-fluorophenyl)-N-(1-(3-(trifluoromethyl)phenylsulfonyl)pyrrolidin-3-yloxy)acetamide (90.0 mg, 65%) as a white solid: LCMS: 433 [M+1]+. 1H NMR (DMSO-d6) δ: 1.88 (m, 1H), 2.04 (m, 1H), 3.37 (m, 3H), 3.54 (d, 1H), 4.55 (s, 1H), 7.29 (t, 2H), 7.76 (m, 2H), 7.87 (t, 1H), 8.06 (t, 2H), 8.15 (d, 1H), 11.6 (s, 1H).

Workup

  1. customquenched with H2O (30 ml)
  2. extractionThe aqueous phase was extracted with ethyl acetate (30 ml×3)
  3. washthe combined organic phase was washed with aqueous 0.1 N HCl solution (20 ml), H2O (30 ml×3) and brine (30 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ethyl acetate/hexane: 33/67)

Sources & evidence

ORD record
ord-6dde4a71e7634df3b313b6e760c5ea1c
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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