Chlorotrimethylsilane → 2-(3-{3-[2-Ethyl-5-hydroxy-4-(3h-imidazol-4-yl)phenoxy]propoxy}-2-propyl-phenoxy)benzoic acid hydrochloride

HRID 1008301ノート

反応式

HRID 1008301 の反応式
C[O:2][C:3](=[O:44])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([O:28]CC3C=CC=CC=3)[C:25]([C:36](=O)[CH3:37])=[CH:24][C:23]=2[CH2:39][CH3:40])[C:12]=1[CH2:41][CH2:42][CH3:43].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].C[Si]([Cl:59])(C)C.Cl[N:61]1[C:65](=O)CCC1=O.[F-].C([N+:73](CCCC)(CCCC)CCCC)CCC>O1CCCC1.CCOCC.O>[ClH:59].[CH2:39]([C:23]1[CH:24]=[C:25]([C:36]2[NH:73][CH:65]=[N:61][CH:37]=2)[C:26]([OH:28])=[CH:27][C:22]=1[O:21][CH2:20][CH2:19][CH2:18][O:17][C:13]1[C:12]([CH2:41][CH2:42][CH3:43])=[C:11]([CH:16]=[CH:15][CH:14]=1)[O:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[C:3]([OH:2])=[O:44])[CH3:40]

参加物

9

反応物 5

HCID 6397ChlorotrimethylsilaneHCID 31398ChlorosuccinimideHCID 2724141Tetrabutylammonium FluorideHCID 2733832Lithium HexamethyldisilazideHCID 601111702-{3-[3-(4-Acetyl-5-benzyloxy-2-ethylphenoxy)propoxy]-2-propyl-phenoxy}benzoic acid methyl ester

生成物 1

HCID 102095352-(3-{3-[2-Ethyl-5-hydroxy-4-(3h-imidazol-4-yl)phenoxy]propoxy}-2-propyl-phenoxy)benzoic acid hydrochloride収率 60%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
0 °C

実験手順

To a solution of 2-{3-[3-(4-acetyl-5-benzyloxy-2-ethylphenoxy)propoxy]-2-propyl-phenoxy}benzoic acid methyl ester (3.04 g, 5.09 mmol) in tetrahydrofuran (50 mL) cooled to −78° C. was added a solution of 1 M lithium hexamethyldisilazide in tetrahydrofuran (11.2 mL, 11.2 mmol) portion wise. After stirring for 20 min, trimethylsilyl chloride (2.6 mL. 20 mmol) was added and the mixture warmed to 0° C. and stirred for 30 min. The mixture was evaporated in vacuo and the residue dissolved in hexane. The resulting solution was filtered and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (50 mL), cooled to 0° C., and treated with N-chlorosuccinimide (750 mg, 5.6 mmol). The mixture was warmed to room temperature and stirred for 30 min, then heated at reflux for 2 h. The mixture was cooled to room temperature and treated with water (4 mL) and a solution of 1 N tetra-n-butylammonium fluoride in tetrahydrofuran (6 mL). After stirring for 15 min the mixture was diluted in ether and washed once with water, once with saturated sodium chloride solution, dried (sodium sulfate), filtered, and concentrated in vacuo. Chromatography (silica gel, 10% ethyl acetate/90% hexane) of the residue provided 1.94 g (60%) of the title compound as a white solid. 1H NMR (CDCl3) δ 7.89 (d, J=8 Hz, 1H), 7.77 (s, 1H), 7.40 (m, 6H), 7.12 (d, J=9 Hz, 1H), 7.06 (d, J=8 Hz, 1H), 6.80 (d, J=8 Hz, 1H), 6.66 (d, J=8 Hz, 1H), 6.49 (s, 1H), 6.43 (d, J=8 Hz, 1H), 5.15 (s, 2H), 4.68.(s, 2H), 4.20 (q, J=6 Hz, 4H), 3.82 (s, 3H), 2.65 (t, J=7 Hz, 2H), 2.59 (q, J=7 Hz, 2H), 2.32 (quintet, J=6 Hz, 2H), 1.54 (hextet, J=8 Hz, 2H), 1.16 (t, J=8 Hz, 3H), 0.89 (t, J=7 Hz, 3H); TOF MS ES+ exact mass calculated for C37H40ClO7 (p+1): m/z=631.2463. Found: 631.2470; IR (CHCl3, cm−1) 2964, 1720, 1603, 1461. Anal. Calcd for C37H39ClO7: C, 70.41; H, 6.23. Found: C, 0.04; H, 5.97.

後処理

  1. stirringstirred for 30 min
  2. customThe mixture was evaporated in vacuo
  3. dissolutionthe residue dissolved in hexane
  4. filtrationThe resulting solution was filtered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in tetrahydrofuran (50 mL)
  7. temperaturecooled to 0° C.
  8. temperatureThe mixture was warmed to room temperature
  9. stirringstirred for 30 min
  10. temperatureheated
  11. temperatureat reflux for 2 h
  12. temperatureThe mixture was cooled to room temperature
  13. stirringAfter stirring for 15 min the mixture
  14. washwashed once with water, once with saturated sodium chloride solution
  15. dry with materialdried (sodium sulfate)
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-acd929924f0e475292d81791669b07fb
出典データセット
uspto-grants-2004_09
特許番号
US06797723B1

反応ノート

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