1-(Chloromethyl)-3,5-bis(trifluoromethyl)benzene → HCID 86677030, compound

HRID 927109Notes

Reaction equation

HRID 927109 reaction equation
[CH2:1]([O:8][C:9]1[N:10]=[N:11][C:12](Cl)=[CH:13][C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Cl[CH2:59][C:60]1[CH:65]=[C:64]([C:66]([F:69])([F:68])[F:67])[CH:63]=[C:62]([C:70]([F:73])([F:72])[F:71])[CH:61]=1.[Mg].[Cl-].[Li+]>O1CCCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Zn].[Cl-].[Zn+2].[Cl-]>[CH2:1]([O:8][C:9]1[N:10]=[N:11][C:12]([CH2:59][C:60]2[CH:61]=[C:62]([C:70]([F:72])([F:73])[F:71])[CH:63]=[C:64]([C:66]([F:67])([F:68])[F:69])[CH:65]=2)=[CH:13][C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

11

Reactant 5

HCID 1235761-(Chloromethyl)-3,5-bis(trifluoromethyl)benzeneHCID 433294Lithium ChlorideHCID 5462224MagnesiumHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 122134743,4-Bis(benzyloxy)-6-chloropyridazine2×

Product 1

HCID 86677030HCID 86677030, compoundYield 33%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 167845palladium(II) acetateCatalystHCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3,4-bis(benzyloxy)-6-chloropyridazine (Intermediate 1) (1 g, 3.06 mmol)dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.143 g, 0.3 mmol) and palladium (II) acetate (0.034 g, 0.15 mmol) in tetrahydrofuran (10 ml) under nitrogen was added the supernatant zinc reagent [generated from the addition of 1-(chloromethyl)-3,5-bis(trifluoromethyl)benzene (3 g, 11.43 mmol) to a suspension of magnesium (0.694 g, 28.6 mmol) in lithium chloride (28.6 ml, 14.28 mmol) in tetrahydrofuran (1M) and zinc(II) chloride (12.57 ml, 12.57 mmol) in tetrahydrofuran, warmed to 30° C. to initiate and stirred for one hour to complete] and the resulting red/brown mixture was heated at 65° C. for 16 hours. The reaction mixture was cooled, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution, saturated aqueous ammonium chloride solution and brine. The organics were dried (MgSO4), filtered and solvent removed in vacuo to give a brown oil. The oil was purified by silica chromatography eluting with 0-40% ethyl acetate in petrol to yield the title compound (520 mg 33%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with saturated aqueous sodium bicarbonate solution, saturated aqueous ammonium chloride solution and brine
  3. dry with materialThe organics were dried (MgSO4)
  4. filtrationfiltered
  5. customsolvent removed in vacuo
  6. customto give a brown oil
  7. customThe oil was purified by silica chromatography
  8. washeluting with 0-40% ethyl acetate in petrol

Sources & evidence

ORD record
ord-7419e22dd563442d9aeb0827d96f65fa
Source dataset
uspto-grants-2016_03
Patent number
US09290456B2

Reaction notes

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