Water → 2-Methyl-2-(4-(pyrimidin-5-yl)phenyl)propanoic acid

HRID 1175591Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.O.[N:15]1[CH:20]=[C:19](B(O)O)[CH:18]=[N:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.[OH-].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:12][C:8]([C:5]1[CH:6]=[CH:7][C:2]([C:19]2[CH:20]=[N:15][CH:16]=[N:17][CH:18]=2)=[CH:3][CH:4]=1)([CH3:13])[C:9]([OH:11])=[O:10]

Participants

Conditions

Temperature: 80 °C

Procedure

2-(4-Bromophenyl)-2-methylpropanoic acid (5.71 g, 23.5 mmol) was dissolved in DME (140 mL) and water (35 mL) and pyrimidin-5-ylboronic acid (2.92 g, 23.5 mmol) and potassium carbonate (11.4 g, 82.2 mmol) were added to the solution. The mixture was degassed using an argon stream, and Pd(PPh3)4 (1.35 g, 1.17 mmol) was added. The mixture was heated (80° C.) under argon overnight then cooled to room temperature. The solution was diluted with 1M NaOH (20 mL) and washed with EtOAc. The aqueous phase was acidified with 6N aq. HCl to pH 4-5 and extracted with EtOAc (3×). The combined extract was successively washed with water and brine, dried over MgSO4, filtered and evaporated to yield 4.2 g (74%) of the crude 2-Methyl-2-(4-(pyrimidin-5-yl)phenyl)propanoic acid (MS+H, 243) that was used in the next step without further purification.

Workup

customThe mixture was degassed
additionwas added
temperaturethen cooled to room temperature
washwashed with EtOAc
extractionextracted with EtOAc (3×)
extractionThe combined extract
washwas successively washed with water and brine
dry with materialdried over MgSO4
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-b0374616427546a294036c938abf74aa
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842324B2

Reaction notes

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