Potassium Bromide → HCID 10220574, compound

HRID 585583Notes

Reaction equation

HRID 585583 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([Cl:10])[CH:3]=1.[F:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=1B(O)O.C([O-])(O)=O.[Na+].[K+].[Br-]>C1(C)C=CC=CC=1.CCO.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>[Cl:10][C:4]1[CH:3]=[C:2]([C:13]2[C:12]([F:11])=[CH:17][CH:16]=[CH:15][C:14]=2[F:18])[CH:9]=[CH:8][C:5]=1[C:6]#[N:7]

Participants

9

Reactant 4

HCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 27343362,6-Difluorophenylboronic acidHCID 70104204-Bromo-2-chlorobenzonitrile

Product 1

HCID 10220574HCID 10220574, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

In an oven-dried flask purged with argon, a solution of 4-bromo-2-chlorobenzonitrile (268 mg, 1.238 mmol), 2,6-difluorophenylboronic acid (293 mg, 1.857 mmol), Pd(PPh3)4 (143 mg, 0.124 mmol) in toluene (10 mL) and EtOH (10 mL), and saturated solution of NaHCO3 in water (1 mL) were refluxed while sterring for 5 h. The reaction mixture was poured into water and extracted 3 times with CH2Cl2. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude compound was then purified by flash cromatography (diethyl ether-hexanes) to provide EM-4977 (45 mg, 15%) as a white solid. IR (KBr): 3072, 2237, 1626, 1602, 1578, 1468, 1386, 1231, 1058, 996, 888, 844, 783, 730, 693, 622, 516 cm−1. 1H RMN (400 MHz, acetone d6) δ 7.23 (t, J=8 Hz, 2H), 7.60 (m, 1H), 7.73 (ddd, J=1.3, 1.4 & 8 Hz, 1H), 7.88 (d, J=1.3 Hz, 1H), 8.07 (d, J=8 Hz, 1H) ppm. 13C RMN (75 MHz, CDCl3) δ 112.06 (d, J=25 Hz), 112.14, 112.85, 115.83, 129.15, 130.80 (t, J=11 Hz), 131.73, 133.63, 135.40, 136.70, 159.63 (dd, J=7 & 250 Hz) ppm. GC/NCI/MS (m/e); 249 (M−, 100).

Workup

  1. customIn an oven-dried flask purged with argon
  2. extractionextracted 3 times with CH2Cl2
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude compound was then purified by flash cromatography (diethyl ether-hexanes)
  7. customto provide EM-4977 (45 mg, 15%) as a white solid

Sources & evidence

ORD record
ord-50bb1f5bb1d4479eb543e4a8d24cd93f
Source dataset
uspto-grants-2005_08
Patent number
US06933321B2

Reaction notes

Loading…