Potassium Carbonate → 4-(Cyclohexen-1-yl)-3-fluoroaniline

HRID 1411412Notes

Reaction equation

HRID 1411412 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1I)[NH2:5].C(=O)([O-])[O-].[K+].[K+].[C:16]1(B2OC(C)(C)C(C)(C)O2)[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]=1>C(COC)OC.O>[C:16]1([C:8]2[CH:7]=[CH:6][C:4]([NH2:5])=[CH:3][C:2]=2[F:1])[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 109326752-(Cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 154755463-Fluoro-4-iodoaniline

Product 1

HCID 666296384-(Cyclohexen-1-yl)-3-fluoroanilineYield 63%

Reagents, catalysts & solvents 1

HCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

In a pressure tube, a solution of 3-fluoro-4-iodoaniline (2.29 g, 9.66 mmol) and potassium carbonate (1.74 g, 12.58 mmol) in 4:1 dimethoxyethane-water (33 mL) was degassed by nitrogen sparge for 40 minutes, followed by addition of 1-cyclohexenyl boronic acid pinacol ester (2.7 mL, 2.61 g, 12.56 mmol). Then 1,1′-bis(diphenylphosphino)ferrocene palladium (II) chloride dichloromethane complex (237 mg, 0.29 mmol) was added followed by degassing for another 5 minutes. The pressure tube was sealed and warmed at 100° C. for 18 hours. The mixture was cooled and diluted with ethyl acetate, followed by extraction with water and saturated sodium chloride solution. The solution was dried (Na2SO4) and stirred with 3-(mercaptopropyl) silica gel for 1 hour. Concentration in vacuo afforded a brown oil, which was chromatographed over a 340 g silica gel cartridge, eluting with 10-100% ethyl acetate in hexanes. These procedures afforded the title compound (1.16 g, 63%) as a light brown oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.00 (m, 1H), 6.37 (m, 2H), 5.84 (s, 1H), 3.71 (br s, 2H), 2.32 (m, 2H), 2.17 (m, 2H), 1.73 (m, 2H), 1.65 (m, 2H); MS (+DCI) m/z (rel abundance) 192 (100, M+H).

Workup

  1. customsparge for 40 minutes
  2. additionThen 1,1′-bis(diphenylphosphino)ferrocene palladium (II) chloride dichloromethane complex (237 mg, 0.29 mmol) was added
  3. customby degassing for another 5 minutes
  4. customThe pressure tube was sealed
  5. temperatureThe mixture was cooled
  6. additiondiluted with ethyl acetate
  7. extractionfollowed by extraction with water and saturated sodium chloride solution
  8. dry with materialThe solution was dried (Na2SO4)
  9. concentrationConcentration in vacuo
  10. customafforded a brown oil, which
  11. customwas chromatographed over a 340 g silica gel cartridge
  12. washeluting with 10-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d519a75201474648b0191680d72707e7
Source dataset
uspto-grants-2014_12
Patent number
US08921514B2

Reaction notes

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