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

HRID 1929582노트

반응식

HRID 1929582 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-951b1f8a88234da5bce0743a93ac9726
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188090B2

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