Cesium carbonate → Methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylate

HRID 1894956Notes

Reaction equation

HRID 1894956 reaction equation
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.Br[C:44]1[CH:45]=[C:46]2[C:51](=[CH:52][CH:53]=1)[N:50]=[CH:49][C:48]([C:54]([O:56][CH3:57])=[O:55])=[CH:47]2.[C:58](=[O:65])([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])[NH2:59].C(=O)([O-])[O-].[Cs+].[Cs+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:61]([O:60][C:58]([NH:59][C:44]1[CH:45]=[C:46]2[C:51](=[CH:52][CH:53]=1)[N:50]=[CH:49][C:48]([C:54]([O:56][CH3:57])=[O:55])=[CH:47]2)=[O:65])([CH3:64])([CH3:63])[CH3:62]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 53465709Methyl 6-bromoquinoline-3-carboxylate

Product 1

HCID 67002181Methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylateYield 76%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a round bottom flask under dry nitrogen were added palladium(II) acetate (100 mg, 0.6 mmol), Xantphos (600 mg, 1 mmol), methyl 6-bromoquinoline-3-carboxylate (1.5 g, 5.64 mmol), t-butyl carbamate (0.99 g, 8.4 mmol) and cesium carbonate (3.67 g, 11.3 mmol). Dry 1,4-dioxane (30 mL) was added by syringe and the mixture was stirred at 100° C. under dry nitrogen for 4 h. The reaction mixture was cooled to room temperature, diluted with water and extracted three times with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude mixture was purified by silica gel chromatography (hexanes to 1:1 hexanes/ethyl acetate gradient) to afford methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylate (Int-2, 1.29 g, 76%). LC-MS: (FA) ES+ 303; 1H NMR (400 MHz, d6-DMSO) δ ppm 9.86 (s, 1H), 9.14 (d, J=2.1 Hz, 1H), 8.82 (d, J=1.9 Hz, 1H), 8.29 (d, J=2.0 Hz, 1H), 8.00 (d, J=9.1 Hz, 1H), 7.87 (dd, J=9.1, 2.4 Hz, 1H), 3.93 (s, 3H), 1.51 (s, 9H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted three times with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude mixture was purified by silica gel chromatography (hexanes to 1:1 hexanes/ethyl acetate gradient)

Sources & evidence

ORD record
ord-9ef9a5547faf4556b681255236d59fbd
Source dataset
uspto-grants-2013_08
Patent number
US08513421B2

Reaction notes

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