Cesium carbonate → HCID 86721322, compound

HRID 2175389Notes

Reaction equation

HRID 2175389 reaction equation
[NH2:1][C:2]1[C:3]([F:11])=[CH:4][C:5](Br)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH:12]1(B(O)O)[CH2:14][CH2:13]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2].O.C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:3]([F:11])=[CH:4][C:5]([CH:12]2[CH2:14][CH2:13]2)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 86721321HCID 86721321, compound

Product 1

HCID 86721322HCID 86721322, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

The product from the above reaction (5-amino-2-bromo-4-fluorobenzonitrile) (4.0 g, 18.6 mmol), cyclo-propyl boronic acid (3.19 g, 37.2 mmol), Pd(OAc)2 (835 mg, 3.72 mmol), tricyclohexyl phosphine (1.04 g, 3.72 mmol), Cs2CO3 (36.3 g, 111.6 mmol) were combined in a pressure vessel. A mixture of toluene (110 ml) and H2O (35 ml) was added. The ensuing yellow-orange suspension was degassed and flushed with nitrogen gas (3×). The pressure vessel was sealed and heated over night (ca. 12 h) at 110° C. After checking the reaction by TLC and HPLC, the precipitate/salts were filtered off, more H2O was added and the mixture was extracted with ethyl acetate (3×). The combined organic phases were filtered through Na2SO4, silica gel was added and solvents were removed using a rotary evaporator. Further purification by CombiFlash (120 g column) eluting with hexanes/ethyl acetate (0→20% gradient) yielded 2.01 g (61%) of the desired product in form of a pale yellow, beige solid. 1H NMR (300 MHz, cdcl3) δ 6.98 (d, J=8.6 Hz, 1H), 6.58 (d, J=12.0 Hz, 1H), 3.81 (s br, 2H), 2.21-2.06 (m, 1H), 1.11-0.99 (m, 2H), 0.69-0.59 (m, 2H); MS (ES) 177 (M+H).

Workup

  1. customwere combined in a pressure vessel
  2. additionwas added
  3. customThe ensuing yellow-orange suspension was degassed
  4. customflushed with nitrogen gas (3×)
  5. customThe pressure vessel was sealed
  6. customthe reaction by TLC and HPLC
  7. filtrationthe precipitate/salts were filtered off
  8. additionmore H2O was added
  9. extractionthe mixture was extracted with ethyl acetate (3×)
  10. filtrationThe combined organic phases were filtered through Na2SO4, silica gel
  11. additionwas added
  12. customsolvents were removed
  13. customa rotary evaporator
  14. customFurther purification by CombiFlash (120 g column)
  15. washeluting with hexanes/ethyl acetate (0→20% gradient)

Sources & evidence

ORD record
ord-a8e162e8729e46bf8300af3a8357a1ff
Source dataset
uspto-grants-2015_06
Patent number
US09062068B2

Reaction notes

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