Propyne → ethyl 8-prop-1-ynyl-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 854908Notes

Reaction equation

HRID 854908 reaction equation
IC1[CH:3]=[C:4]([O:21][C:22]([F:25])([F:24])[F:23])[CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:15])([F:14])[F:13])[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7]2.[CH2:26](Cl)Cl.[CH:29]#[C:30][CH3:31]>C1(C)C=CC=CC=1.[Cl-].[Na+].O.[Cu]I.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]>[C:30]([C:31]1[CH:3]=[C:4]([O:21][C:22]([F:25])([F:23])[F:24])[CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:13])([F:14])[F:15])[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7]2)#[C:29][CH3:26]

Participants

8

Reactant 3

HCID 6335Propyne2×HCID 6344Dichloromethane2×HCID 86599457ethyl 8-iodo-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 86599459ethyl 8-prop-1-ynyl-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 89%

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+)Catalyst2×HCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a Parr bottle containing a mixture of ethyl 8-iodo-6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate prepared as in Example 21 a, Step 2 (0.500 g, 1.04 mmole), CuI (20 mg, 0.104 mmole), PdCl2(dppf)2.CH2Cl2 (84.5 mg, 0.104 mmole) and TEA (434 uL, 3.11 mmole) in anhydrous toluene (10 mL) was added at −78° C. propyne (2 ml) and the bottle was sealed. After stirring for 23 h at room temperature, an additional propyne (5 ml) was added and the mixture was stirred an additional 23 h at room temperature. Additional PdCl2(dppf)2.CH2Cl2 (120 mg, 0.147 mmole) was added and the mixture was stirred at room temperature for an additional 24 h. The mixture was then poured into brine (100 mL) and extracted with EtOAc (200 mL). The EtOAc layer was separated, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica chromatography (9:1 hexanes:EtOAc) to give 0.363 g (89% yield) of the product as a yellow crystalline solid: EIHRMS m/z 394.0644 (M+, C17H12F6O4, Calc'd 394.0640).

Workup

  1. additionTo a Parr bottle containing
  2. customthe bottle was sealed
  3. stirringthe mixture was stirred an additional 23 h at room temperature
  4. stirringthe mixture was stirred at room temperature for an additional 24 h
  5. extractionextracted with EtOAc (200 mL)
  6. customThe EtOAc layer was separated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica chromatography (9:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-2455429601cd4ea0a35f009180254359
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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