Hydrogen chloride-ethyl acetate → 8-Chloro-3-(4-methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octane

HRID 1295500ノート

反応式

HRID 1295500 の反応式
[CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]([CH2:7][N:8]2[CH2:14][CH:13]3[C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=4)(O)[CH:10]([CH2:11][CH2:12]3)[CH2:9]2)=[CH:5][CH:4]=1.[ClH:27].CCOC(C)=O>CCOC(C)=O>[Cl:27][C:15]1([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=2)[CH:13]2[CH2:12][CH2:11][CH:10]1[CH2:9][N:8]([CH2:7][C:6]1[CH:25]=[CH:26][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[CH2:14]2

参加物

4

反応物 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 694310753-(4-Methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octan-8-ol

生成物 1

HCID 694314818-Chloro-3-(4-methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octane

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

3-(4-Methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octan-8-ol (1.48 g, 4.19 mmol) was dissolved in EtOAc (20 mL), charged with 2.5N HCl/EtOAc (6 mL), and azeotroped with MeOH (2×50 mL) to yield the HCl salt. This salt was slurried in CH2Cl2 (20 mL) and pyridine (0.34 mL, 4.19 mmol) then treated with thionyl chloride (0.92 mL, 12.6 mmol) dropwise, causing the dispersion to dissolve. The reaction was judged complete by TLC after 2 h, at which time it was carefully added to 1N NaOH (50 mL) at 0° C., bringing the final pH to 9. The product was extracted with CH2Cl2 (3×20 mL), washed with saturated aqueous NaCl solution (1×50 mL), filtered through a cotton plug and concentrated to brown oil. Flash chromatography provided a white solid (1.31 g, 84%). (TLC 40% EtOAc/hexanes Rf 0.75); 1H NMR (400 MHz, CDCl3) δ 7.23 (m, 3H), 7.04 (d, J=7.5 Hz, 1H), 6.99 (s, 1H), 6.84 (d, J=8.7 Hz, 2H), 6.79 (dd, J=7.9, 2.1 Hz, 1H), 3.78 (s, 6H), 3.53 (br s, 2H), 2.95 (d, J=10.3 Hz, 2H), 2.67 (br s, 2H), 2.65 (m, 2H), 1.79 (d, J=1.0 Hz, 2H), 1.45 (m, 2H); LCMS m/z 372.2 (M+1)+; mp 99–102° C.

後処理

  1. customazeotroped with MeOH (2×50 mL)

出典と根拠

ORDレコード
ord-94abec4de4ac4af2bca99025d039732c
出典データセット
uspto-grants-2007_07
特許番号
US07241887B2

反応ノート

読み込み中…