Toluene → 5-[3-(4-Bromo-phenyl)-benzo[d]isothiazol-6-yl]-pent-4-yn-1-ol

HRID 270321Notes

Reaction equation

HRID 270321 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15](OS(C(F)(F)F)(=O)=O)=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[CH2:32]([OH:37])[CH2:33][CH2:34][C:35]#[CH:36].C(N(CC)CC)C>C1COCC1.CCOC(C)=O.OS([O-])(=O)=O.[K+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([C:36]#[C:35][CH2:34][CH2:33][CH2:32][OH:37])=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1

Participants

11

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 793464-Pentyn-1-ol2×HCID 57428076Trifluoro-methanesulfonic acid 3-(4-bromo-phenyl)-benzo[d]isothiazol-6-yl ester

Product 1

HCID 223140325-[3-(4-Bromo-phenyl)-benzo[d]isothiazol-6-yl]-pent-4-yn-1-olYield 72%

Reagents, catalysts & solvents 6

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent4×HCID 8857Ethyl AcetateSolventHCID 516920Potassium bisulfateSolvent

Procedure

3.0 g (6.846 mmol) Trifluoro-methanesulfonic acid 3-(4-bromo-phenyl)-benzo[d]isothiazol-6-yl ester were suspended three times with toluene prior to the reaction, then dissolved in 25 ml THF and added to 240 mg (0.34 mmol) PdCl2(PPh3)2. To this suspension 0.67 ml (7.19 mmol) 4-pentyn-1-ol in 1 ml THF were added, followed by 54 mg (0.205 mmol) triphenylphosphine in 1 ml THF and 2.9 ml (20.54 mmol) triethylamine. The solution was stirred for 20 min at RT prior to the addition of 13 mg (0.07 mmol) CuI. The solution was heated to 50° C. overnight. Further 132 μl (1.4 mmol) 4-pentyn-1-ol in 0.8 ml THF were added in two portions and stirring at 50° C. was continued for 5 h and at RT over night. The reaction mixture was diluted with EtOAc and 1M KHSO4. The inorganic phase was extracted with EtOAc and the combined organic phases were washed with water and brine and dried over Na2SO4. Column chromatography with a gradient hexane:EtOAc 2:1 to 1:1 gave 1.83 g (72%) 5-[3-(4-Bromo-phenyl)-benzo[d]isothiazol-6-yl]-pent-4-yn-1-ol as light yellow oil, MS: 371 (M, 1Br).

Workup

  1. customto the reaction
  2. temperatureThe solution was heated to 50° C. overnight
  3. stirringstirring at 50° C.
  4. waitwas continued for 5 h and at RT over night
  5. extractionThe inorganic phase was extracted with EtOAc
  6. washthe combined organic phases were washed with water and brine
  7. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-7a9d29709fcd44dca8ebf02b1cc498fe
Source dataset
uspto-grants-2008_11
Patent number
US07449483B2

Reaction notes

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