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 929257Notes

Reaction equation

HRID 929257 reaction equation
[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

Participants

7

Reactant 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×

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-6f53d8227f9248d7ad230de82d7585d1
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

Loading…