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 929259Notes

Reaction equation

HRID 929259 reaction equation
[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

Participants

9

Reactant 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-purine2×

Product 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

Reagents, catalysts & solvents 4

HCID 23985GoldCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
85 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-1270e38575ba445dba462cff6a46ec77
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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