반응 #422837

ord-6a279c94609e4da189b71d03bae10ad2

용매

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    여과After 36h at room temperature the reaction mixture was filtered through a glass-filter
  2. 2
    기타The filtrate was evaporated in vaccuo
  3. 3
    기타Purification by silica gel chromatography

실험 절차

To a stirred solution of 4-chlorobenzoyl chloride (1.0 g, 5.8 mmol) and 1,3-dimethoxybenzene (788.5 mg, 5.8 mmol) in CH2Cl2 (150 mL) at 0° C. was added AlCl3 (841.5 mg, 6.4 mmol). The reaction mixture was warmed to room temperature. After 12h the reaction mixture was poured into aq. NaHCO3 and extracted with CH2Cl2 (twice). The combined extracts were washed with brine, dried over Na2SO4, and concentrated in vaccuo to provide a 1:1 mixture of(4-chlorophenyl)(2-hydroxy-4-methoxyphenyl)methanone and (4-chlorophenyl)(2,4-dimethoxyphenyl)methanone. Purification by silica gel chromatography provided methoxyphenyl)methanone (650 mg, 2.5 mmol) and (4-chlorophenyl)(2,4-dimethoxyphenyl)methanone(700 mg, 2.5 mmol). The combined molecules (2.7 g) were dissolved in AcOH (50 mL) and 49% HBr (50 mL) was added. After 12h at 90° C. all volatiles were evaporated in vaccuo to afford (4-chlorophenyl)(2,4-dihydroxyphenyl)methanone in quantitative yield. Without purification this was subjected to alkylation with 1,8-dibromooctane (4.0 g, 14.7 mmol) and K2CO3 (2.0 g, 14.7 mmol) in DMF (50 mL). After 12 h the reaction mixture was diluted with water (150 mL) and the water phase was extracted with EtOAc (twice). The combined organic phase was washed with brine, dried over Na2SO4, and concentrated in vaccuo to give the crude product. Purification by silica gel chromatography provided (4-(8-bromooctyloxy)-2-hydroxyphenyl)(4-chlorophenyl)methanone(1.9 g, 4.4 mmol). To a stirred solution of (4-(8-bromooctyloxy)-2-hydroxyphenyl)(4-chlorophenyl)methanone (1.9 g, 4.4 mmol) in THF (25 mL) was added N-methylprop-2-en-1-amine (938.1 mg, 13.2 mmol) and NaHCO3 (13.2 mmol). After 36h at room temperature the reaction mixture was filtered through a glass-filter. The filtrate was evaporated in vaccuo. Purification by silica gel chromatography provided (4-(8-(allyl(methyl)amino)octyloxy)-2-hydroxyphenyl)(4-chlorophenyl)methanone (1.8 g, 1.9 mmol); 1H-NMR (300 MHz, CDCl3) 12.6 ppm (s, 1H) , 7.64 (d, J=9.6 Hz, 2H), 7.60-7.48 (m, 3H), 6.59 ( s, 1H), 6.45 (d, J=9.6 Hz, 1H), 6.05-5.84 (m, 1H), 5.39-5.12 (m, 2H), 4.05 (t, J=7.7 Hz, 2H), 3.21-2.99 (m, 2H), 2.51-2.11 (m, 7H), 1.92-1.80 (m, 2H), 1.79-1.21(m, 8H); 13C-NMR (75 MHz, CDCl3) 196.3 ppm, 162.5, 138.1, 137.8, 134.2, 132.3, 131.7, 128.5, 110.9, 101.8, 68,8, 60.4, 57.0. 43.8, 29.6, 29.3, 27.3, 28.1; ESI-MS calcd for C25H33ClNO3 [M+H+]: 430.2. found 430.2.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08884061B2uspto-grants-2014_11