Tricyclohexylphosphine → HCID 59295455, compound

HRID 2233309Notes

Reaction equation

HRID 2233309 reaction equation
Br[C:2]1[CH:9]=[C:8]([CH2:10][O:11][CH:12]([C:17]2[S:21][C:20]([C:22]3[CH:23]=[N:24][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:27]=3)=[N:19][C:18]=2[CH3:32])[C:13]([F:16])([F:15])[F:14])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].FC(F)(F)C(C1S[C:40]([C:42]2[CH:43]=NC(C(F)(F)F)=CC=2)=NC=1C)O.BrC1C=C(CBr)C=CC=1C#N.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C1(B(O)O)CC1>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[CH:43]1([C:2]2[CH:9]=[C:8]([CH2:10][O:11][CH:12]([C:17]3[S:21][C:20]([C:22]4[CH:23]=[N:24][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:27]=4)=[N:19][C:18]=3[CH3:32])[C:13]([F:14])([F:16])[F:15])[CH:7]=[CH:6][C:3]=2[C:4]#[N:5])[CH2:42][CH2:40]1

Participants

9

Reactant 5

HCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 534255212-Bromo-4-(bromomethyl)benzonitrileHCID 59295410HCID 59295410, compoundHCID 59295451HCID 59295451, compound

Product 1

HCID 59295455HCID 59295455, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

309 mg 2-Bromo-4-{2,2,2-trifluoro-1-[4-methyl-2-(6-trifluoromethyl-pyridin-3-yl)-thiazol-5-yl]-ethoxymethyl}-benzonitrile (derived from 2,2,2-Trifluoro-1-[4-methyl-2-(6-trifluoromethyl-pyridin-3-yl)-thiazol-5-yl]-ethanol and 2-Bromo-4-bromomethyl-benzonitrile according to the method described in example 30), 32 mg tricyclohexylphosphine, 148 mg cyclopropylboronic acid and 470 mg K3PO4 mono hydrate were dissolved in a mixture of 4 ml toluene and 0.4 ml water. The reaction mixture was purged with argon, then 130 mg palladium (II) acetate were added. The reaction mixture was stirred at 100° C. for three hours. The cooled reaction mixture was diluted by addition of 100 ml ethyl acetate and filtered through a celite pad. The filtrate was washed twice with 25 ml water, then dried over MgSO4. The solvent was removed in vacuo. The resulting residue was purified by reversed phase HPLC to obtain 185 mg 2-Cyclopropyl-4-{2,2,2-trifluoro-1-[4-methyl-2-(6-trifluoromethyl-pyridin-3-yl)-thiazol-5-yl]-ethoxymethyl}-benzonitrile.

Workup

  1. customThe reaction mixture was purged with argon
  2. addition130 mg palladium (II) acetate were added
  3. customThe cooled reaction mixture
  4. filtrationfiltered through a celite pad
  5. washThe filtrate was washed twice with 25 ml water
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed in vacuo
  8. customThe resulting residue was purified by reversed phase HPLC

Sources & evidence

ORD record
ord-ba606e0effa149cf89184e9540bd50f1
Source dataset
uspto-grants-2010_05
Patent number
US07709481B2

Reaction notes

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