Water → HCID 67980966, compound

HRID 2407019Notes

Reaction equation

HRID 2407019 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH:8]([OH:13])[CH2:9][CH:10]([CH3:12])[CH3:11])=[CH:4][N:3]=1.[F:14][C:15]([F:26])([F:25])[C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.[F-].[K+].O>C1(C)C=CC=CC=1.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>[CH3:11][CH:10]([CH3:12])[CH2:9][CH:8]([C:5]1[CH:4]=[N:3][C:2]([C:19]2[CH:20]=[CH:21][C:16]([C:15]([F:26])([F:25])[F:14])=[CH:17][CH:18]=2)=[N:7][CH:6]=1)[OH:13]

Participants

7

Reactant 4

HCID 962WaterHCID 522689Potassium FluorideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 86667308HCID 86667308, compound

Product 1

HCID 67980966HCID 67980966, compoundYield 14.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

To a solution of the 1-(2-chloropyrimidin-5-yl)-3-methylbutan-1-ol (600 mg, 2.99 mmol) in toluene (15.0 mL) was added Pd(PPh3)4 (346 mg, 0.299 mmol), 4-(trifluoromethyl)phenyl boronic acid (682 mg, 3.59 mmol), potassium fluoride (521 mg, 8.97 mmol) and water (3.7 mL). The reaction mixture was purged with nitrogen and heated to reflux for 5 h. The phases were separated and the aqueous layer was extracted with ethyl acetate (3×200 mL). The combined organic layers were concentrated under reduced pressure. The crude solid was purified by silics gel chromatography to give 3-methyl-1-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)butan-1-ol (138 mg) as a yellow solid. 1HNMR (400 MHz, CDCl3) δ 8.77 (s, 2H), 8.55 (d, J=8.4 Hz, 2H), 7.68 (d, J=8.4 Hz, 2H), 4.81-4.84 (m, 1H), 1.92-1.65 (m, 2H), 1.53-1.47 (m, 1H), 0.94 (d, J=6.4 Hz, 6H).

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. temperatureheated
  3. temperatureto reflux for 5 h
  4. customThe phases were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×200 mL)
  6. concentrationThe combined organic layers were concentrated under reduced pressure
  7. customThe crude solid was purified by silics gel chromatography

Sources & evidence

ORD record
ord-6bb984fd1e254b7e9c5ced24cce2c9d8
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Reaction notes

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