Benzene, 1-bromo-4-(trifluoromethyl)- → 4-Tetrahydropyranyloxy-4'-trifluormethyltolan

HRID 1359184Notes

Reaction equation

HRID 1359184 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[CH:15])=[CH:10][CH:9]=1.Br[C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=1>C(NC(C)C)(C)C.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>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]#[C:15][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 2

HCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 11310191P-[Tetrahydropyran-2-yloxy]phenylacetylene

Product 1

HCID 582885584-Tetrahydropyranyloxy-4'-trifluormethyltolan

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 7912DiisopropylamineSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 3 (12.1 g, 60 mmol) and 4-bromobenzotriflouride (14.85 g, 66 mmol) in diisopropylamine (250 ml) was heated to 30° C. under nitrogen, and the solution was degassed. Then Pd(PPh3)2Cl2 (210 mg, 0.3 mmol) and copper(I) iodide (114 mg, 0.6 mmol) were added to this clear solution. The reaction mixture was stirred for 2 hours at 80° C., then cooled to room temperature. The salt formed during the reaction procedure was filtered off and washed well with ethyl acetate. The filtrate was evaporated to dryness and hydrolyzed with concentrated hydrochloric acid (10 ml), water (100 ml) and crushed ice (50 g), then extracted with ethyl acetate. The combined organic paste was washed with brine and dried over MgSO4. The solvent was removed in vacuo and the residue was purified by column chromatography (petroleum ether-ethyl acetate=9:1) to give a pale yellow crystals of 4. Yield 16.6 g (80%); mp 112˜113° C.; δHCDCl3; 300 MHz): 7.59(s, 4H, Ar—H), 7.48(d, J=8.7, 2H, Ar—H), 7.04(d, J=8.7, 2H, Ar—H), 5.46(t, J=3.1, 1H, OCHO), 3.89(m, 1H, THP), 3.62(m, 1H, THP), 1.86˜1.62(m, 6H, THP).

Workup

  1. customthe solution was degassed
  2. temperaturecooled to room temperature
  3. customThe salt formed during the reaction procedure
  4. filtrationwas filtered off
  5. washwashed well with ethyl acetate
  6. customThe filtrate was evaporated to dryness and hydrolyzed with concentrated hydrochloric acid (10 ml), water (100 ml)
  7. customcrushed ice (50 g)
  8. extractionextracted with ethyl acetate
  9. washThe combined organic paste was washed with brine
  10. dry with materialdried over MgSO4
  11. customThe solvent was removed in vacuo
  12. customthe residue was purified by column chromatography (petroleum ether-ethyl acetate=9:1)
  13. customto give a pale yellow crystals of 4

Sources & evidence

ORD record
ord-6053ac4fe7e546419e8f7e8f31bd3d13
Source dataset
uspto-grants-2003_07
Patent number
US06599945B2

Reaction notes

Loading…