Triphenylphosphine → 2-Chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-benzonitrile

HRID 1172683Notes

Reaction equation

HRID 1172683 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[S:5][C:6]=1[CH:7]([OH:9])[CH3:8].[Cl:20][C:21]1[CH:28]=[C:27](O)[CH:26]=[CH:25][C:22]=1[C:23]#[N:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[Cl:20][C:21]1[CH:28]=[C:27]([O:9][CH:7]([C:6]2[S:5][C:4]([C:10]3[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=3)=[N:3][C:2]=2[CH3:1])[CH3:8])[CH:26]=[CH:25][C:22]=1[C:23]#[N:24]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5927972-Chloro-4-hydroxybenzonitrileHCID 5462977Diethyl azodicarboxylateHCID 226476311-[4-Methyl-2-(4-trifluoromethylphenyl)thiazol-5-yl]ethanol

Product 1

HCID 595563342-Chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-benzonitrileYield 71.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2.0 g 1-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethanol and 1.18 g 2-chloro-4-hydroxybenzonitrile were dissolved in 50 ml tetrahydrofuran. At −20° C. 2.74 g triphenylphosphine and 1.82 g diethylazodicarboxylate were added. The cooling bath was removed and the reaction mixture stirred at room temperature for four hours. Then the reaction mixture was poured on 100 ml ice cold saturated NH4Cl solution and extracted five times with portions of 80 ml ethyl acetate. The combined organic layers were washed with 100 ml brine then dried over MgSO4. The solvent was evaporated in vacuo and the resulting residue purified by chromatography on silica gel with the eluent n-heptane: ethyl acetate=4:1 to obtain 2.1 g 2-chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-benzonitrile as pale yellow solid.

Workup

  1. customAt −20° C
  2. customThe cooling bath was removed
  3. additionThen the reaction mixture was poured on 100 ml ice cold saturated NH4Cl solution
  4. extractionextracted five times with portions of 80 ml ethyl acetate
  5. washThe combined organic layers were washed with 100 ml brine
  6. dry with materialthen dried over MgSO4
  7. customThe solvent was evaporated in vacuo
  8. customthe resulting residue purified by chromatography on silica gel with the eluent n-heptane

Sources & evidence

ORD record
ord-4dae2ff26a55499d86d215cafde86ac8
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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