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

HRID 1866510노트

반응식

HRID 1866510 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-8dd50e6d5baf4582ac9d6c3e338a054c
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07629358B2

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