Sodium Carbonate → (3R,3aR,6R,6aR)-6-(6-Chloro-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazo[4,5-b]pyridin-2-yloxy)hexahydrofuro[3,2-b]furan-3-ol

HRID 1485605Notes

Reaction equation

HRID 1485605 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:11]=[C:10]([O:12][C@H:13]3[C@H:17]4[O:18][CH2:19][C@@H:20]([OH:21])[C@H:16]4[O:15][CH2:14]3)[N:9]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:5]2=[N:6][C:7]=1I.[B:30]1([C:39]2[CH:44]=[CH:43][C:42](B3OC(C)(C)C(C)(C)O3)=[CH:41][CH:40]=2)[O:34][C:33]([CH3:36])([CH3:35])[C:32]([CH3:38])([CH3:37])[O:31]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[N:11]=[C:10]([O:12][C@H:13]3[C@H:17]4[O:18][CH2:19][C@@H:20]([OH:21])[C@H:16]4[O:15][CH2:14]3)[N:9]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:5]2=[N:6][C:7]=1[C:42]1[CH:43]=[CH:44][C:39]([B:30]2[O:34][C:33]([CH3:36])([CH3:35])[C:32]([CH3:38])([CH3:37])[O:31]2)=[CH:40][CH:41]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 105924952,2'-(1,4-Phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)HCID 123413447(3R,3aR,6R,6aR)-6-(6-chloro-5-iodo-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-2-yloxy)hexahydrofuro[3,2-b]furan-3-ol

Product 1

HCID 123678375(3R,3aR,6R,6aR)-6-(6-Chloro-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazo[4,5-b]pyridin-2-yloxy)hexahydrofuro[3,2-b]furan-3-ol

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (3R,3aR,6R,6aR)-6-(6-chloro-5-iodo-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazo[4,5-b]pyridin-2-yloxy)hexahydrofuro[3,2-b]furan-3-ol (2.00 g), 1,4-benzenediboronic acid dipinacol ester (2.38 g), Na2CO3 (2 M aqueous solution, 5.42 mL), and 1,4-dioxane (15 mL) is purged for 5 minutes with argon. [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium(II)-CH2Cl2-complex (PdCl2(dppf)×CH2Cl2) (206 mg) is added and the mixture is stirred over night at 70° C. The reaction mixture is partitioned between water and ethyl acetate. The organic phase is washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel (dichloromethane/methanol 99:1→97:3) to give the title compound. LC (method 1): tR=1.27 min; Mass spectrum (ESI+): m/z=630 [M+H]+.

Workup

  1. customis purged for 5 minutes with argon
  2. addition[1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium(II)-CH2Cl2-complex (PdCl2(dppf)×CH2Cl2) (206 mg) is added
  3. customThe reaction mixture is partitioned between water and ethyl acetate
  4. washThe organic phase is washed with water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue is chromatographed on silica gel (dichloromethane/methanol 99:1→97:3)

Sources & evidence

ORD record
ord-c901f2022b654015919ab977c53935e1
Source dataset
uspto-grants-2016_08
Patent number
US09422312B2

Reaction notes

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