1-(4-Fluorophenyl)piperazine → {6-Fluoro-4-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3-methyl-naphthalen-2-yl}-acetic acid methyl ester

HRID 1929582Notes

Reaction equation

HRID 1929582 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:8]([CH3:15])=[C:9]2[C:12]([OH:14])=O)=[CH:4][CH:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH3:20][O:19][C:17](=[O:18])[CH2:16][C:7]1[C:8]([CH3:15])=[C:9]([C:12]([N:31]2[CH2:30][CH2:29][N:28]([C:25]3[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=3)[CH2:33][CH2:32]2)=[O:14])[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=2)[CH:6]=1

Participants

7

Reactant 4

HCID 752601-(4-Fluorophenyl)piperazineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 593267347-Fluoro-3-methoxycarbonylmethyl-2-methyl-naphthalene-1-carboxylic acid

Product 1

HCID 59326707{6-Fluoro-4-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3-methyl-naphthalen-2-yl}-acetic acid methyl esterYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-fluoro-3-methoxycarbonylmethyl-2-methyl-naphthalene-1-carboxylic acid (27.6 mg, 0.10 mmol) and 1-(4-fluoro-phenyl)-piperazine (19.8 mg, 0.11 mmol) in N,N-dimethylformamide (2 mL) was added bromo-tris-pyrrolidino phosphonium hexafluorophosphate (46.6 mg, 0.10 mmol) and N,N-diisopropylethylamine (34.7 μL, 0.20 mmol). After being stirred at room temperature for 24 hours, the resulting mixture was diluted with ethyl acetate (10 mL), and washed with 1N hydrochloric acid (10 mL), a saturated aqueous solution of sodium carbonate (10 mL), and brine (10 mL). The resulting organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (gradient elution with 20-40% ethyl acetate in petroleum ether) to afford {6-fluoro-4-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (36.2 mg, 83%) as a white solid.

Workup

  1. washwashed with 1N hydrochloric acid (10 mL)
  2. dry with materialThe resulting organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (gradient elution with 20-40% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-951b1f8a88234da5bce0743a93ac9726
Source dataset
uspto-grants-2012_05
Patent number
US08188090B2

Reaction notes

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