Cesium carbonate → HCID 178453999, compound

HRID 906050Notes

Reaction equation

HRID 906050 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].CC([N:24]([C@H:28]1[CH2:33][CH2:32][C@H:31]([NH2:34])[CH2:30][CH2:29]1)[C:25](=[O:27])[O-:26])(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:41][C:42]1(C)[C:68]2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:43]1=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].O.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:34][C@H:31]1[CH2:30][CH2:29][C@H:28]([NH:24][C:25]([O:26][C:42]([CH3:68])([CH3:43])[CH3:41])=[O:27])[CH2:33][CH2:32]1)#[N:19]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67404157Benzyl 3-bromo-4-cyanobenzoateHCID 178449843HCID 178449843, compound

Product 1

HCID 178453999HCID 178453999, compoundYield 500%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A pressure vessel containing a magnetic stirbar was charged with phenylmethyl 3-bromo-4-cyanobenzoate (100 mg, 0.32 mmol), 1,1-dimethylethyl(trans-4-aminocyclohexyl)carbamate (69 mg, 0.32 mmol), cesium carbonate (125 mg, 0.38 mmol), XANTPHOS (19 mg, 0.032 mmol), tris(dibenzylideneacetone)dipalladium(0) (15 mg, 0.016 mmol) and dioxane (1.5 mL). The vessel was then sealed and heated to 95° C. The suspension was stirred for approximately 24 h at that temperature and was then allowed to cool to room temperature. The suspension was poured into water, and the resulting aqueous mixture was extracted twice with ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was then purified by column chromatography (4:1 hexanes:ethyl acetate) to provide impure phenylmethyl 4-cyano-3-{[trans-4-({[(1,1-dimethylethyl)oxy]carbonyl}-amino)cyclohexyl]amino}benzoate (71.8 mg, 0.16 mmol) as a yellow powder. This material was carried into the subsequent step without further purification. 1H NMR (400 MHz, CDCl3): 7.45-7.28 (m, 8H), 5.37 (s, 2H), 4.47 (m, 1H), 3.40 (m, 1H), 2.12 (m, 4H), 1.46 (s, 9H), 1.31 (m, 4H).

Workup

  1. additionA pressure vessel containing a magnetic stirbar
  2. customThe vessel was then sealed
  3. temperatureto cool to room temperature
  4. extractionthe resulting aqueous mixture was extracted twice with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was then purified by column chromatography (4:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-af551a4d8b954a8e8ced059947cfe65d
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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