Potassium Phosphate, Tribasic → HCID 90067172, compound

HRID 929146Notes

Reaction equation

HRID 929146 reaction equation
[CH2:1]([N:4]1[C:12]2[C:7](=[N:8][C:9](I)=[C:10]([Cl:13])[CH:11]=2)[N:6]=[C:5]1[O:15][C@@H:16]1[CH2:20][O:19][C@@H:18]2[C@H:21]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:22][O:23][C@H:17]12)[CH:2]=[CH2:3].[Br:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CCOC(C)=O.CCCCCC>O1CCOCC1.O>[CH2:1]([N:4]1[C:12]2[C:7](=[N:8][C:9]([C:36]3[CH:37]=[CH:38][C:33]([Br:32])=[CH:34][CH:35]=3)=[C:10]([Cl:13])[CH:11]=2)[N:6]=[C:5]1[O:15][C@@H:16]1[CH2:20][O:19][C@@H:18]2[C@H:21]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:22][O:23][C@H:17]12)[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 79599(4-Bromophenyl)boronic acidHCID 21226206Ethyl acetate hexane2×HCID 123197088HCID 123197088, compound

Product 1

HCID 90067172HCID 90067172, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Palladium tetrakistriphenylphosphine (204.6 mg, 0.177 mmol) was added to a stirred suspension of [(3R,3aR,6R,6aS)-3-(1-allyl-6-chloro-5-iodo-imidazo[4,5-b]pyridin-2-yl)oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy-tert-butyl-dimethyl-silane (1.0083 g, 1.745 mmol), 4-bromophenylboronic acid (385.9 mg, 1.922 mmol), and tripotassium phosphate (1.1412 g, 5.38 mmol) in dioxane (14.0 ml) and water (3.5 ml). The reaction mixture was degassed (3×) and placed under nitrogen before being heated to 100° C. for 16 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (150 ml) and water (150 ml). The aqueous layer was extracted with EtOAc (2×75 ml). The organic layers were combined, washed with brine (1×75 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to give a yellow foam. Flash chromatography of the foam utilizing a 80 g silica RediSep Rf® column and employing a 0-30% EtOAc/hexane gradient followed by 30% EtOAc/hexane afforded the title compound as a yellow foam. LC-MS: calculated for C27H33BrClN3O4Si 605.11, 607.11 observed m/e: 606.20, 608.16 (M+H)+ (Rt 1.47/2 min)

Workup

  1. customThe reaction mixture was degassed (3×)
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between EtOAc (150 ml) and water (150 ml)
  4. extractionThe aqueous layer was extracted with EtOAc (2×75 ml)
  5. washwashed with brine (1×75 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give a yellow foam

Sources & evidence

ORD record
ord-377fc142943947bdabc9f717a77977a1
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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