Potassium Phosphate, Tribasic → US10023592, Example 254

HRID 575730Notes

Reaction equation

HRID 575730 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:8][C:7]=2B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.Br[C:26]1[C:27]2[CH:36]=[CH:35][O:34][C:28]=2[C:29](=[O:33])[N:30]([CH3:32])[CH:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([S:12]([CH3:15])(=[O:13])=[O:14])=[CH:8][C:7]=2[C:26]2[C:27]3[CH:36]=[CH:35][O:34][C:28]=3[C:29](=[O:33])[N:30]([CH3:32])[CH:31]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180214004-Bromo-6-methylfuro[2,3-c]pyridin-7-oneHCID 1234348592-[2-(Cyclopropylmethoxy)-5-(methylsulfonyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 118021115US10023592, Example 254Yield 49%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (115 mg, 0.33 mmol), 4-bromo-6-methyl-6H,7H-furo[2,3-c]pyridin-7-one (75 mg, 0.33 mmol), K3PO4 (175 mg, 0.83 mmol), Pd(dppf)Cl2 (24 mg, 10%) in dioxane/H2O (2.2 mL/200 uL) was bubbled with nitrogen for 5 min. The sealed vial was stirred at 70° C. for 90 min. The reaction mixture was filtered through a short plug of celite; the celite plug was washed with EtOAc (15 mL). The filtrate was washed with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford a brown residue. The resulting residue was purified by prep-HPLC to afford the title compound (60 mg, 49%) as a white solid. LCMS (M+H)+=374.

Workup

  1. customwas bubbled with nitrogen for 5 min
  2. filtrationThe reaction mixture was filtered through a short plug of celite
  3. washthe celite plug was washed with EtOAc (15 mL)
  4. washThe filtrate was washed with water and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a brown residue
  9. customThe resulting residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-78bfcbc08c63455587c8a3ed1df2d8df
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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