Ethyl Acetate → 6-([1,1'-biphenyl]-4-yl)-2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-c]pyridine

HRID 929257ノート

反応式

HRID 929257 の反応式
[Si:1]([O:8][C@H:9]1[C@H:13]2[O:14][CH2:15][C@@H:16]([O:17][C:18]3[N:27]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:21]4[CH:22]=[N:23][C:24](Cl)=[CH:25][C:20]=4[N:19]=3)[C@H:12]2[O:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([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>[C:36]1([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:41]=[CH:40][C:39]([C:24]2[N:23]=[CH:22][C:21]3[N:27]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:33])([CH3:35])[CH3:34])[C:18]([O:17][C@@H:16]4[CH2:15][O:14][C@@H:13]5[C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])[CH2:10][O:11][C@H:12]45)=[N:19][C:20]=3[CH:25]=2)=[CH:38][CH:37]=1

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 1512531,1'-Biphenyl-4-yl-boronic acidHCID 900421802-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-c]pyridine2 回

生成物 1

HCID 900423086-([1,1'-biphenyl]-4-yl)-2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-c]pyridine

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
85 °C

実験手順

Palladium tetrakistriphenylphosphine (42.6 mg, 0.037 mmol) was added to a stirred suspension of 2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-c]pyridine (Intermediate 46, 100.0 mg, 0.184 mmol), 4-biphenylboronic acid (54.8 mg, 0.277 mmol), and potassium phosphate tribasic (117.0 mg, 0.553 mmol) in degassed 20% water in dioxane (1.44 mL). The reaction mixture stirred under N2 at 85° C. After 2 h, more palladium tetrakistriphenylphosphine (42.6 mg, 0.037 mmol) was added. The reaction mixture heated under N2 at 85° C. for another 7 h, then cooled to room temperature and the lower aqueous layer was drawn off and discarded. The remaining reaction mixture was added to EtOAc (50 mL), filtered, and the resulting solids were washed with EtOAc (2×15 mL). The filtrate was evaporated under reduced pressure. Flash chromatography of the resulting residue utilizing a 24 g silica RediSep Rf® Gold column and employing a 0-100% EtOAc/hexane gradient afforded the title compound. LC-MS: calculated for C36H49N3O5Si2 659.32 observed m/e: 660.13 (M+H)+ (Rt 1.58/2.0 min).

後処理

  1. temperatureThe reaction mixture heated under N2 at 85° C. for another 7 h
  2. temperaturecooled to room temperature
  3. customThe remaining reaction mixture
  4. filtrationfiltered
  5. washthe resulting solids were washed with EtOAc (2×15 mL)
  6. customThe filtrate was evaporated under reduced pressure

出典と根拠

ORDレコード
ord-6f53d8227f9248d7ad230de82d7585d1
出典データセット
uspto-grants-2016_03
特許番号
US09290517B2

反応ノート

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