Tetrahydrofuran → HCID 49793320, compound

HRID 2369371Notes

Reaction equation

HRID 2369371 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].O1CCCC1.I[C:13]1[S:17][CH:16]=[N:15][C:14]=1[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22].[C:26]([C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1)#[CH:27]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I.C(OCC)C.C(Cl)Cl>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C:26]#[C:27][C:13]2[S:17][CH:16]=[N:15][C:14]=2[NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:29][CH:30]=1

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 5226271-Ethynyl-4-fluorobenzeneHCID 49793319HCID 49793319, compound

Product 1

HCID 49793320HCID 49793320, compoundYield 85.7%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

2.93 g (9 mmol) of caesium carbonate are dried in an evacuated Schlenk flask under temperature, and 50 ml of dry tetrahydrofuran, 978 mg (3.00 mmol) of tert-butyl N-(5-iodo-1,3-thiazol-4-yl)carbamate, 396 mg (3.30 mmol) of 1-ethynyl-4-fluorobenzene, 122 mg (0.15 mmol) of Pd(dppf)2Cl2.CH2Cl2 and 57 mg (0.30 mmol) of CuI are subsequently added under nitrogen. The reaction mixture is heated at 50° C. for 6 h, subsequently cooled and filtered through Celite, and the solvent is removed in vacuo. The residue is taken up with ethyl acetate and washed with saturated NaCl solution. The combined organic phases are dried over sodium sulfate, evaporated in vacuo, and the residue is purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1/1), giving 820 mg (2.57 mmol, 85%) of tert-butyl N-{5-[2-(4-fluorophenyl)ethynyl]-1,3-thiazol-4-yl}carbamate as yellow solid from diethyl ether;

Workup

  1. temperaturesubsequently cooled
  2. filtrationfiltered through Celite
  3. customthe solvent is removed in vacuo
  4. washwashed with saturated NaCl solution
  5. dry with materialThe combined organic phases are dried over sodium sulfate
  6. customevaporated in vacuo
  7. customthe residue is purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1/1)

Sources & evidence

ORD record
ord-ee2cc5f9843d4f9baaeb59b35055cc43
Source dataset
uspto-grants-2014_04
Patent number
US08703961B2

Reaction notes

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