Lithium Hydroxide → (3R,3aR,6R,6aR)-6-((5-([1,1'-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

HRID 929149Notes

Reaction equation

HRID 929149 reaction equation
[Li+].[OH-].Br[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:15]=[C:14]3[N:16]=[C:17]([O:27][C@H:28]4[C@H:32]5[O:33][CH2:34][C@@H:35]([OH:36])[C@H:31]5[O:30][CH2:29]4)[N:18]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:13]3=[CH:12][C:11]=2[Cl:37])=[CH:6][CH:5]=1.[C:38]1(B(O)O)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O1CCOCC1.O>[Cl:37][C:11]1[CH:12]=[C:13]2[N:18]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:17]([O:27][C@H:28]3[C@H:32]4[O:33][CH2:34][C@@H:35]([OH:36])[C@H:31]4[O:30][CH2:29]3)=[N:16][C:14]2=[N:15][C:10]=1[C:7]1[CH:8]=[CH:9][C:4]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 66827Phenylboronic AcidHCID 86684749HCID 86684749, compound

Product 1

HCID 89558893(3R,3aR,6R,6aR)-6-((5-([1,1'-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

LiOH (1.3 ml, 3.90 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (107.7 mg, 0.132 mmol) were added to a stirred solution of (3R,3aR,6R,6aR)-6-[5-(4-bromophenyl)-6-chloro-1-(2-trimethylsilylethoxymethyl)-imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (776.2 mg, 1.332 mmol) and phenylboronic acid (201.9 mg, 1.656 mmol) in dioxane (10.5 ml) and water (1.3 ml). The reaction mixture was degassed (3×) and placed under nitrogen before being heated to 80° C. for 20 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (100 ml) and water (100 ml). The aqueous layer was extracted with EtOAc (2×50 ml). The organic layers were combined, washed with brine (1×30 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give an amber residue. This material was purified by flash chromatography, utilizing a 40 g silica RediSep Rf® column and employing a 0-70% EtOAc/hexane gradient followed by 70% EtOAc/hexane. The product fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a yellow solid. LC-MS: calculated for C30H34ClN3O5Si 579.2 observed m/e: 580.24 (M+H)+ (Rt 1.36/2 min).

Workup

  1. customThe reaction mixture was degassed (3×)
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between EtOAc (100 ml) and water (100 ml)
  4. extractionThe aqueous layer was extracted with EtOAc (2×50 ml)
  5. washwashed with brine (1×30 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give an amber residue
  10. customThis material was purified by flash chromatography
  11. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-14dfb053cea6400b87aac5f7fb50726e
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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