Cesium carbonate → Ethyl 4-cyano-3-(pentan-3-ylamino)benzoate

HRID 906174Notes

Reaction equation

HRID 906174 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[C:13]#[N:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:21][CH2:22][CH:23]([NH2:26])[CH2:24][CH3:25].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>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:13]([C:12]1[CH:11]=[CH:10][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3][C:2]=1[NH:26][CH:23]([CH2:24][CH3:25])[CH2:22][CH3:21])#[N:14]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 120193-PentanamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 18374323Ethyl 3-bromo-4-cyanobenzoate

Product 1

HCID 67402973Ethyl 4-cyano-3-(pentan-3-ylamino)benzoateYield 61.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

To a pressure vessel were added ethyl 3-bromo-4-cyanobenzoate (500 mg, 1.97 mmol), cesium carbonate (1.28 g, 3.94 mmol), pentan-3-amine (688 uL, 5.90 mmol), XANTPHOS (114 mg, 0.20 mmol), tris(dibenzylideneacetone)dipalladium(0) (90 mg, 0.10 mmol), and dioxane (3 mL). The vessel was sealed and heated to 95° C. for 15 h. After cooling to room temperature, the mixture was filtered through celite and the filter cake rinsed with ethyl acetate. The filtrate was then concentrated and the residue was purified by column chromatography (10% ethyl acetate in hexanes) to provide ethyl 4-cyano-3-(pentan-3-ylamino)benzoate (315 mg, 1.21 mmol, 61% yield) as a yellow syrup. 1H NMR (400 MHz, CDCl3): 7.43 (d, 1H), 7.33 (s, 1H), 7.25 (dd, 1H), 4.44-4.35 (m, 3H), 3.48-3.40 (m, 1H), 1.72-1.48 (m, 4H), 1.40 (t, 3H), 0.96 (t, 6H); MS (EI) for C15H20N2O2: 261 (MH+).

Workup

  1. customThe vessel was sealed
  2. temperatureAfter cooling to room temperature
  3. filtrationthe mixture was filtered through celite
  4. washthe filter cake rinsed with ethyl acetate
  5. concentrationThe filtrate was then concentrated
  6. customthe residue was purified by column chromatography (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-33a35fad81244927ab87bc72fcdaf14d
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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