Ethyl Acetate → 2-([1,1'-biphenyl]-4-yl)-8-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-purine

HRID 929259노트

반응식

HRID 929259 반응식
[C:1]([Si:5]([CH3:35])([CH3:34])[O:6][C@H:7]1[C@H:11]2[O:12][CH2:13][C@@H:14]([O:15][C:16]3[N:24]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:23]4[C:18](=[N:19][C:20](Cl)=[N:21][CH:22]=4)[N:17]=3)[C@H:10]2[O:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2].[C:36]1([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CCOC(C)=O>O.O1CCOCC1.[Au].CCOC(C)=O.CCCCCC>[C:36]1([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:41]=[CH:40][C:39]([C:20]2[N:19]=[C:18]3[C:23]([N:24]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:31])[CH3:32])[C:16]([O:15][C@@H:14]4[CH2:13][O:12][C@@H:11]5[C@H:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:34])[CH3:35])[CH2:8][O:9][C@H:10]45)=[N:17]3)=[CH:22][N:21]=2)=[CH:38][CH:37]=1

참가 물질

9

반응물 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 1512531,1'-Biphenyl-4-yl-boronic acidHCID 900415468-(((3R,3aR,6R,6aS)-6-((tert-butyldimethyl-silyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-2-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-purine2회

생성물 1

HCID 900419412-([1,1'-biphenyl]-4-yl)-8-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-purine

시약·촉매·용매 4

HCID 23985Gold촉매HCID 962Water용매HCID 312751,4-Dioxane용매HCID 21226206Ethyl acetate hexane용매

반응 조건

온도
85 °C

실험 절차

Palladium tetrakistriphenylphosphine (21.3 mg, 0.018 mmol) was added to a stirred suspension of 8-(((3R,3aR,6R,6aS)-6-((tert-butyldimethyl-silyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-2-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-purine (Intermediate 47, 50.0 mg, 0.092 mmol), 4-biphenylboronic acid (27.3 mg, 0.138 mmol), and potassium phosphate tribasic (58.6 mg, 0.276 mmol) in degassed 20% water in dioxane (0.72 mL). The reaction mixture stirred under N2 at 85° C. for 2.5 h, then additional more palladium tetrakistriphenylphosphine (21.3 mg, 0.018 mmol) was added. The reaction mixture heated under N2 at 85° C. for another 3.5 h and then cooled to room temperature. The lower aqueous layer was drawn off and discarded. The remaining reaction mixture was added to EtOAc (25 mL), and filtered. The resulting solids were washed with EtOAc (2×10 mL). The filtrate was evaporated under reduced pressure to give a residue. Flash chromatography of the resulting residue utilizing a 12 g silica RediSep Rf® Gold column and employing a 0-80% EtOAc/hexane gradient afforded the title compound. LC-MS: calculated for C35H48N4O5Si2 660.32 observed m/e: 661.61 (M+H)+ (Rt 1.85/2.0 min).

후처리

  1. temperatureThe reaction mixture heated under N2 at 85° C. for another 3.5 h
  2. temperaturecooled to room temperature
  3. customThe remaining reaction mixture
  4. filtrationfiltered
  5. washThe resulting solids were washed with EtOAc (2×10 mL)
  6. customThe filtrate was evaporated under reduced pressure
  7. customto give a residue

출처 및 근거

ORD 기록
ord-1270e38575ba445dba462cff6a46ec77
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290517B2

반응 노트

불러오는 중…