Cyclohexylamine → Benzyl 4-cyano-3-(cyclohexylamino)benzoate

HRID 906146Notes

Reaction equation

HRID 906146 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[C:18]#[N:19])[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[CH:26]1([NH2:32])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:18]([C:17]1[CH:16]=[CH:15][C:4]([C:5]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6])=[CH:3][C:2]=1[NH:32][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)#[N:19]

Participants

8

Reactant 4

HCID 7965CyclohexylamineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67404157Benzyl 3-bromo-4-cyanobenzoate

Product 1

HCID 67405391Benzyl 4-cyano-3-(cyclohexylamino)benzoateYield 75%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a pressure vessel were added benzyl 3-bromo-4-cyanobenzoate (150 mg, 0.47 mmol) prepared as described in example 11 (steps 1, 2), cesium carbonate (310 mg, 0.95 mmol), cyclohexylamine (108 uL, 0.95 mmol), XANTPHOS (27 mg, 0.047 mmol), tris(dibenzylideneacetone)dipalladium(0) (21 mg, 0.023 mmol), and dioxane (3 mL). The vessel was sealed and heated to 95° C. for 4 h. After cooling to room temperature, the mixture was diluted with ethyl acetate and was washed with water. The aqueous phase was extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography (10% ethyl acetate in hexanes) to provide benzyl 4-cyano-3-(cyclohexylamino)benzoate (118 mg, 0.35 mmol, 75% yield) as a yellow syrup. 1H NMR (400 MHz, CDCl3): 7.45-7.30 (m, 7H), 7.27 (dd, 1H), 5.36 (s, 2H), 4.56 (d, 1H), 3.48-3.38 (m, 1H), 2.08-2.01 (m, 2H), 1.83-1.75 (m, 2H), 1.71-1.64 (m, 1H), 1.46-1.35 (m, 2H), 1.31-1.20 (m, 3H); MS (EI) for C21H22N2O2: 333 (M−H).

Workup

  1. customprepared
  2. customThe vessel was sealed
  3. temperatureAfter cooling to room temperature
  4. washwas washed with water
  5. extractionThe aqueous phase was extracted with ethyl acetate
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a741229b11624418815c947ba60379a8
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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