Cesium carbonate → Ethyl 2-(1-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroquinolin-7-yl)-5-(3-chloropropyl)thiazole-4-carboxylate

HRID 1896578Notes

Reaction equation

HRID 1896578 reaction equation
Br[C:2]1[S:3][C:4]([CH2:12][CH2:13][CH2:14][Cl:15])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.CC1(C)C(C)(C)OB([C:24]2[CH:33]=[C:32]3[C:27]([CH2:28][CH2:29][CH2:30][N:31]3[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[CH:26][CH:25]=2)O1.[Cl-].[Li+].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:37]([O:36][C:34]([N:31]1[C:32]2[C:27](=[CH:26][CH:25]=[C:24]([C:2]3[S:3][C:4]([CH2:12][CH2:13][CH2:14][Cl:15])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=3)[CH:33]=2)[CH2:28][CH2:29][CH2:30]1)=[O:35])([CH3:40])([CH3:38])[CH3:39]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 433294Lithium ChlorideHCID 59418661Ethyl 2-bromo-5-(3-chloropropyl)thiazole-4-carboxylateHCID 59418664tert-butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 59418759Ethyl 2-(1-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroquinolin-7-yl)-5-(3-chloropropyl)thiazole-4-carboxylateYield 81.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl 2-bromo-5-(3-chloropropyl)thiazole-4-carboxylate (23C) (0.790 g, 2.5 mmol) was dissolved in dioxane, the tert-butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (23E) (0.910 g, 2.5 mmol) was added followed by lithium chloride (0.320 g, 7.6 mmol), tetrakis(triphenylphosphine)palladium(0) (0.290 g, 0.25 mmol), cesium carbonate (2.5 g, 7.6 mmol) and water. This was transferred to a sealed tube, the reaction was evacuated, flushed with nitrogen and heated at 100° C. overnight. The reaction was filtered through Celite, eluted with EtOAc, concentrated under reduced pressure, and dry loaded onto silica. The crude material was purified by column chromatography on silica gel eluting with a gradient of 0 to 50% EtOAc in hexanes to provide 0.943 g (80%) of the desired product ethyl 2-(1-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroquinolin-7-yl)-5-(3-chloropropyl)thiazole-4-carboxylate (23F): LC/MS (APCI): m/z 466.1 (M+H).

Workup

  1. customThis was transferred to a sealed tube
  2. customthe reaction was evacuated
  3. customflushed with nitrogen
  4. filtrationThe reaction was filtered through Celite
  5. washeluted with EtOAc
  6. concentrationconcentrated under reduced pressure
  7. customdry
  8. customThe crude material was purified by column chromatography on silica gel eluting with a gradient of 0 to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-deb112bdcb884e9b80b8889d729a64bd
Source dataset
uspto-grants-2013_08
Patent number
US08518970B2

Reaction notes

Loading…