Potassium Phosphate, Tribasic → US10023592, Example 323

HRID 575787Notes

Reaction equation

HRID 575787 reaction equation
Br[C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[C:4]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[CH3:22][N:23]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[C:25]([CH3:38])[C:24]1=[O:39].[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]>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][O:12][C:4]2[CH:3]=[C:2]([C:27]3[CH:26]=[C:25]([CH3:38])[C:24](=[O:39])[N:23]([CH3:22])[CH:28]=3)[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=2)=[CH:15][CH:16]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 57863085Bromo-3-methanesulfonyl-5-(4-methoxy-benzyloxy)-benzeneHCID 712703091,3-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridin-2-one

Product 1

HCID 118021456US10023592, Example 323Yield 83.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 1-bromo-3-[(4-methoxyphenyl)methoxy]-5-methylsulfonylbenzene (450 mg, 1.2 mmol), 1,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (300 mg, 1.2 mmol), Pd(dppf)Cl2 (88 mg) and K3PO4 (654 mg, 3 mmol) in dioxane (8 mL) and water (800 uL) was purged with nitrogen for 7 min, capped, and heated to 75° C. for 1 h. After the mixture was filtered through a short bed of celite, the filtrate was concentrated in vacuo and purified by silica gel column chromatography using a gradient of EtOAc (5 to 100%) in DCM to afford the title compound (416 mg, 83%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.05-2.14 (s, 3H) 3.25-3.28 (s, 3H) 3.49-3.57 (s, 3H) 3.74-3.81 (s, 3H) 5.12-5.22 (s, 2H) 6.93-7.03 (m, 2H) 7.34-7.47 (m, 3H) 7.52-7.59 (m, 1H) 7.64-7.72 (m, 1H) 7.82-7.90 (m, 1H) 8.14-8.22 (m, 1H). LCMS (M+H)+=414.

Workup

  1. customwas purged with nitrogen for 7 min
  2. customcapped
  3. filtrationAfter the mixture was filtered through a short bed of celite
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-0f65aec056814e089d17621f1de7be4d
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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