Tetrahydrofuran → 2-{1-[2-(2,4-difluorophenyl)ethyl]azetidin-3-yl}-N,N-dimethoxyacetamide

HRID 10217

反応式

HRID 10217 の反応式
CO[C:3](=[O:19])[CH2:4][CH:5]1[CH2:8][N:7]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[F:18])[CH2:6]1.Cl.C[NH:22][O:23][CH3:24].C([Mg]Cl)(C)C.[Cl-].[NH4+].[O:32]1CCC[CH2:33]1>>[F:18][C:12]1[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:11]=1[CH2:10][CH2:9][N:7]1[CH2:6][CH:5]([CH2:4][C:3]([N:22]([O:32][CH3:33])[O:23][CH3:24])=[O:19])[CH2:8]1

参加物

6

反応物 5

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 21978392Methyl{1-[2-(2,4-difluorophenyl)ethyl]azetidin-3-yl}acetateHCID 178418918HCID 178418918、化合物

生成物 1

HCID 219783682-{1-[2-(2,4-difluorophenyl)ethyl]azetidin-3-yl}-N,N-dimethoxyacetamide収率 54%

反応条件

温度
-20 °C

実験手順

A slurry of methyl{1-[2-(2,4-difluorophenyl)ethyl]azetidin-3-yl}acetate (Step 1, 0.5 g, 1.86 mmol) and N,O-dimethylhydroxylamine hydrochloride (272 mg, 2.79 mmol) in tetrahydrofuran (4 mL) was cooled to −20° C. under nitrogen. Isopropylmagnesium chloride (2M in tetrahydrofuran, 2.79 mL, 5.57 mmol) was added dropwise, maintaining the internal temperature between −20 and −5° C. The reaction was stirred at −20° C. for 30 minutes then at room temperature for 2.5 hours. Saturated ammonium chloride solution was added and the mixture stirred vigorously for 5 minutes then extracted with ethyl acetate (x3). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 7% methanol/dichloromethane, to give 2-{1-[2-(2,4-difluorophenyl)ethyl]azetidin-3-yl}-N,N-dimethoxyacetamide (297 mg, 54%). 1H NMR (400 MHz, CDCl3) δ 7.16–7.10 (1H, m), 6.79–6.71 (2H, m), 3.67 (3H, s), 3.51–3.47 (2H, m), 3.14 (3H, s), 2.89–2.79 (3H, m), 2.71 (2H, d, J=6.8 Hz), 2.62 (4H, s); m/z (ES+) 299 (M+H)+.

後処理

  1. temperaturemaintaining the internal temperature between −20 and −5° C
  2. waitat room temperature for 2.5 hours
  3. stirringthe mixture stirred vigorously for 5 minutes
  4. extractionthen extracted with ethyl acetate (x3)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica
  8. washeluting with 7% methanol/dichloromethane

出典と根拠

ORDレコード
ord-2a9066dffd474d6f87e1d6731d6c6d43
出典データセット
uspto-grants-2006_08
特許番号
US07094777B2

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