Potassium Phosphate, Tribasic → 3-Cyclopropyl-4-methoxybenzonitrile

HRID 1675951Notes

Reaction equation

HRID 1675951 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[C:5]#[N:6].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:20]1(B(O)O)[CH2:22][CH2:21]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:20]1([C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=2[O:10][CH3:11])[C:5]#[N:6])[CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 7360493-Bromo-4-methoxybenzonitrileHCID 2760897Cyclopropylboronic acid2×

Product 1

HCID 574847073-Cyclopropyl-4-methoxybenzonitrile

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-bromo-4-methoxybenzonitrile (8-1, 5.0g, 23.6 mmol, 1.0 eq), aqueous potassium phosphate tribasic (65.0 ml, 1.27 M, 3.5 eq), cyclopropylboronic acid (10.1 g, 118 mmol, 5.0 eq), Pd(OAc)2 (0.539 g, 2.36 mmol, 0.1 eq) and tricyclohexylphosphine (0.661 g, 2.36 mmol, 0.1 eq) was stirred in degassed toluene (103 ml) and heated to 80° C. for three hours. An additional amount of cyclopropylboronic acid (1.0 g, 1.16 mmol, 0.5 eq) was added and the solution was further heated for 16 hours at 80° C. to complete the reaction. The reaction mixture was cooled and partitioned between brine and EtOAc. The organic phase was dried over sodium sulfate, filtered and concentrated to give an orange oil. The oil was purified by normal phase column chromatography (0 to 10% EtOAc in hexanes) to afford the product (8-2) as a yellow oil. 1H NMR (CDCl3) δ 7.44 (dd, 1H, J=8.4, 2.0 Hz), 7.09 (d, 1H, J=2.0 Hz), 6.86 (d, 1H, J=8.4 Hz), 3.92 (s, 3H), 2.13 (m, 1H), 0.97 (m, 2H), 0.65 (m, 2H).

Workup

  1. temperaturethe solution was further heated for 16 hours at 80° C.
  2. customthe reaction
  3. temperatureThe reaction mixture was cooled
  4. custompartitioned between brine and EtOAc
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an orange oil
  9. customThe oil was purified by normal phase column chromatography (0 to 10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a0cbaf5024824f51b28523059e8a0245
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

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