Sodium Iodide → 3-{2-[(2R)-2-(4-benzyloxy-3-hydroxymethyl-phenyl)-2-(tert-butyldimethyl-silanyloxy)ethylamino]-2-methylpropyl}benzoic acid methyl ester

HRID 1866510ノート

反応式

HRID 1866510 の反応式
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][C:11]([NH2:14])([CH3:13])[CH3:12])[CH:5]=1.[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([C@@H:30]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH2:31]Br)=[CH:26][C:25]=1[CH2:41][OH:42])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[I-].[Na+].C(N(C(C)C)CC)(C)C>C(#N)C>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][C:11]([NH:14][CH2:31][C@@H:30]([C:27]2[CH:28]=[CH:29][C:24]([O:23][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[C:25]([CH2:41][OH:42])[CH:26]=2)[O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])([CH3:12])[CH3:13])[CH:5]=1

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanolHCID 57516949Methyl 3-(2-amino-2-methylpropyl)benzoate

生成物 1

HCID 579782283-{2-[(2R)-2-(4-benzyloxy-3-hydroxymethyl-phenyl)-2-(tert-butyldimethyl-silanyloxy)ethylamino]-2-methylpropyl}benzoic acid methyl ester

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

3-(2-amino-2-methylpropyl)benzoic acid methyl ester (Preparation 34) (1.36 g, 6.60 mmol), [2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol (Preparation 23) (2.96 g, 6.60 mmol), sodium iodide (980 mg, 6.60 mmol) and diisopropylethylamine (3.44 ml, 19.7 mmol) in acetonitrile (10 ml) were heated to reflux for 48 hours under a nitrogen atmosphere. The solvent was then removed in vacuo and saturated aqueous sodium hydrogen carbonate solution (20 ml) added and the product extracted with ethyl acetate (3×30 ml). The combined organics were washed with brine (3×20 ml), dried (sodium sulfate) and the solvent removed in vacuo. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 by volume) to furnish the title compound, the purified product was dissolved in diethylether and evaporated (×3) to yield a white foam (1.70 g).

後処理

  1. temperatureto reflux for 48 hours under a nitrogen atmosphere
  2. customThe solvent was then removed in vacuo and saturated aqueous sodium hydrogen carbonate solution (20 ml)
  3. additionadded
  4. extractionthe product extracted with ethyl acetate (3×30 ml)
  5. washThe combined organics were washed with brine (3×20 ml)
  6. dry with materialdried (sodium sulfate)
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 by volume)

出典と根拠

ORDレコード
ord-8dd50e6d5baf4582ac9d6c3e338a054c
出典データセット
uspto-grants-2009_12
特許番号
US07629358B2

反応ノート

読み込み中…