HCID 54263873, compound → HCID 22918525, compound

HRID 1376815Notes

Reaction equation

HRID 1376815 reaction equation
Cl[C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([O:16][C:17]([F:20])([F:19])[F:18])[CH:13]=[CH:12][C:11]=2[O:21][CH3:22])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:23]1([Mg]Br)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1(P([Ni-](Cl)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCC1>[CH3:22][O:21][C:11]1[CH:12]=[CH:13][C:14]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:15][C:10]=1[CH2:9][NH:8][C:7]1[C:2]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 54263873HCID 54263873, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 22918525HCID 22918525, compoundYield 51.1%

Reagents, catalysts & solvents 2

HCID 178479587HCID 178479587, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
4 °C

Procedure

To a 250 mL 3 neck round bottom flask equipped with a mechanical stirrer, thermometer, addition funnel, and nitrogen inlet, were charged 98.1 mL of tetrahydrofuran, 3.27 grams (9.83 mmoles) of the 2-chloro-3-(2-methoxy-5-trifluoromethoxybenzylamino) pyridine and 1.93 grams (2.95 mmoles) of bis(triphenylphosphino)nickel(II) chloride. The black reaction mixture was stirred at 25 degree celsius for 40 minutes. Phenylmagnesium bromide (1M/THF, 38.4 mL, 38.4 mmoles) was added over a 25 minute period and the resulting black slurry was stirred for 2 hours at 25 degree celsius. During this time, the reaction was monitored by thin layer chromatography assay. The reaction mixture was cooled to 4° C., and quenched with 5.89 mL acetic acid. The reaction mixture was vacuum concentrated to a low volume and partitioned between 100 mL each of toluene and water. The organic layer was washed several times with water and concentrated to an oil. The oil was purifid by column chromatography to yield 1.88 grams (51.1%) of the desired material (as an oil). The structure of this compound was assigned on the basis of high resolution NMR. 1H NMR (CDC13) 8.05 (d, 1H), 7.63 (d, 2H), 7.45 (m, 3H), 7.12 (bs, 1H), 7.08 (m, 2H), 6.93 (dd, 1H), 6.85 (d, 1H), 4.71 (t, 1H), 4.26 (d, 2H), 3.78 (s, 3H).

Workup

  1. additionthermometer, addition funnel, and nitrogen inlet
  2. customThe black reaction mixture
  3. stirringthe resulting black slurry was stirred for 2 hours at 25 degree celsius
  4. customquenched with 5.89 mL acetic acid
  5. concentrationconcentrated to a low volume
  6. custompartitioned between 100 mL each of toluene and water
  7. washThe organic layer was washed several times with water
  8. concentrationconcentrated to an oil

Sources & evidence

ORD record
ord-3f255ba1e94d4bc1b13cfcf262e59028
Source dataset
uspto-grants-1997_09
Patent number
US05663349

Reaction notes

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