Potassium Phosphate, Tribasic → US10023592, Example 258

HRID 575743Notes

Reaction equation

HRID 575743 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=1[O:13][CH2:14][C:15]([F:18])([F:17])[F:16].[CH3:19][N:20]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[C:23]2[CH:35]=[CH:36][O:37][C:22]=2[C:21]1=[O:38].[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]>[CH3:19][N:20]1[CH:25]=[C:24]([C:2]2[CH:7]=[C:6]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:5]=[CH:4][C:3]=2[O:13][CH2:14][C:15]([F:18])([F:17])[F:16])[C:23]2[CH:35]=[CH:36][O:37][C:22]=2[C:21]1=[O:38]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180220292-Bromo-4-((methylsulfonyl)methyl)-1-(2,2,2-trifluoroethoxy)benzeneHCID 1240169906-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furo[2,3-c]pyridin-7-one

Product 1

HCID 118021941US10023592, Example 258Yield 33.2%

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-bromo-4-(methylsulfonylmethyl)-1-(2,2,2-trifluoroethoxy)benzene (100 mg, 0.29 mmol), 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furo[2,3-c]pyridin-7-one (96 mg, 0.35 mmol), K3PO4 (184 mg, 0.87 mmol), Pd(dppf)Cl2 (22 mg, 10%) in dioxane/H2O (2 mL/1 mL) was bubbled with nitrogen for 5 min. The sealed vial was heated to 70° C. for 2 h. 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. The resulting residue was purified by prep-HPLC to afford the title compound (40 mg, 33%) as an off-white solid. 1H NMR (CDCl3, 400 MHz) δ 7.76 (d, J=2.0 Hz, 1H) 7.53 (d, J=2.0 Hz, 1H) 7.41-7.38 (m, 1H) 7.37 (s, 1H) 7.02 (d, J=8.4, 1H) 6.72 (d, J=2.0 Hz, 2H) 4.37 (q, J=8.0 Hz, 2H) 4.27 (s, 2H) 3.73 (s, 3H) 2.89 (s, 3H). LCMS (M+H)+=416.

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. customThe resulting residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-04ea1a16424640759e3dda53d4148c54
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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