Tetrahydrofuran → Methyl 2-(2-((2-(methylthio)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)acetate

HRID 2272402Notes

Reaction equation

HRID 2272402 reaction equation
I[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([S:12][CH3:13])[N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[CH2:41][C:42]([O:44][CH3:45])=[O:43])#[CH:34].C1COCC1>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.C(N(CC)CC)C>[CH3:13][S:12][C:4]1[N:3]=[C:2]([C:34]#[C:33][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[CH2:41][C:42]([O:44][CH3:45])=[O:43])[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 45789861Methyl 2-(2-ethynylphenyl)acetateHCID 717433934-Iodo-2-(methylthio)-5-(trifluoromethyl)pyrimidine

Product 1

HCID 68282774Methyl 2-(2-((2-(methylthio)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)acetateYield 69%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

4-Iodo-2-(methylthio)-5-(trifluoromethyl)pyrimidine (I12) (2.00 g, 6.24 mmol), PdCl2(PPh3)2 (438 mg, 625 μmol), CuI (119 mg, 625 μmol) and triphenylphosphine (164 mg, 625 μmol) were placed into an oven dried microwave reaction vial under nitrogen. Methyl 2-(2-ethynylphenyl)acetate (I4) (1.31 g, 7.49 mmol), THF (20 mL) and triethylamine (10 mL) were added and the resulting mixture was stirred at 100° C. under microwave irradiation for 10 min. The volatiles were evaporated under reduced pressure then the residue was adsorbed onto silica from DCM. The pre-adsorbed material was chromatographed on silica gel (6-25% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I13) (1.571 g, 69%) as an orange solid; 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J=0.8 Hz, 1H), 7.68 (dd, J=7.7, 1.1 Hz, 1H), 7.50-7.29 (m, 3H), 3.93 (s, 2H), 3.71 (d, J=3.4 Hz, 3H), 2.62 (d, J=3.4 Hz, 3H).

Workup

  1. customdried
  2. custommicrowave reaction vial under nitrogen
  3. customThe volatiles were evaporated under reduced pressure
  4. customThe pre-adsorbed material was chromatographed on silica gel (6-25% ethyl acetate/petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-27f1bf57dfb3436e8483c12d4607059f
Source dataset
uspto-grants-2015_09
Patent number
US09120761B2

Reaction notes

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