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

HRID 1948568Notes

Reaction equation

HRID 1948568 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 (5.0 g, 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 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-ae4f2c98f52b405c9a0561796238fb85
Source dataset
uspto-grants-2013_03
Patent number
US08399494B2

Reaction notes

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