3-Fluorophenylboronic acid → Ethyl 2-tert-butyl-4-(3-fluorophenyl)pyrimidine-5-carboxylate

HRID 1930376Notes

Reaction equation

HRID 1930376 reaction equation
C([O-])(O)=O.[Na+].C1(C)C=CC=CC=1.C(O)C.[C:16]([C:20]1[N:25]=[C:24](Cl)[C:23]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:22][N:21]=1)([CH3:19])([CH3:18])[CH3:17].[F:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1>CCOC(C)=O.O.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>[C:16]([C:20]1[N:25]=[C:24]([C:37]2[CH:36]=[CH:35][CH:34]=[C:33]([F:32])[CH:38]=2)[C:23]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:22][N:21]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 3

HCID 27339863-Fluorophenylboronic acidHCID 24903912Ethyl 2-(tert-butyl)-4-chloropyrimidine-5-carboxylateHCID 86620166NaHCO3 toluene ethanol

Product 1

HCID 69296296Ethyl 2-tert-butyl-4-(3-fluorophenyl)pyrimidine-5-carboxylateYield 72%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

In a mix of sat'd NaHCO3:toluene:ethanol (1:2:1) (8 mL) was dissolved ethyl 2-tert-butyl-4-chloropyrimidine-5-carboxylate from Example B40 (300 mg, 1.24 mmol), 3-fluorophenylboronic acid (350 mg, 2.47 mmol) and to this was added tetrakis(triphenylphosphine)palladium(0) (29 mg). The mixture was heated overnight at 75° C. under Ar. The mixture was diluted with EtOAc (25 mL) and water (25 mL). The mixture was filtered to remove insolubles and the organic phase separated, washed with 5% citric acid (25 mL), then saturated sodium bicarbonate (25 mL) and brine (25 mL). The solvents evaporated at reduced pressure and the residue purified by silica gel column chromatography (Biotage: 25M, 5-50% EtOAc/Hex—550 mL) to give ethyl 2-tert-butyl-4-(3-fluorophenyl)pyrimidine-5-carboxylate (0.27 g, 72% yield).

Workup

  1. filtrationThe mixture was filtered
  2. customto remove insolubles
  3. customthe organic phase separated
  4. washwashed with 5% citric acid (25 mL)
  5. customThe solvents evaporated at reduced pressure
  6. customthe residue purified by silica gel column chromatography (Biotage: 25M, 5-50% EtOAc/Hex—550 mL)

Sources & evidence

ORD record
ord-f5c34bd126e5435f8e35fd0d5d91f38a
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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