Dichloromethane → 3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester

HRID 886341Notes

Reaction equation

HRID 886341 reaction equation
CC1(C)COB([C:8]2[CH:29]=[CH:28][C:11]3[C:12]4[N:16]([CH2:17][CH2:18][O:19][C:10]=3[CH:9]=2)[CH:15]=[C:14]([C:20]2[N:21]([CH:25]([CH3:27])[CH3:26])[N:22]=[CH:23][N:24]=2)[N:13]=4)OC1.C(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+].[C:40]([O:44][C:45]([N:47]1[CH:52]2[CH2:53][CH2:54][CH:48]1[CH:49]=[C:50](OS(C(F)(F)F)(=O)=O)[CH2:51]2)=[O:46])([CH3:43])([CH3:42])[CH3:41]>COCCOC.O>[C:40]([O:44][C:45]([N:47]1[CH:52]2[CH2:53][CH2:54][CH:48]1[CH:49]=[C:50]([C:8]1[CH:29]=[CH:28][C:11]3[C:12]4[N:16]([CH2:17][CH2:18][O:19][C:10]=3[CH:9]=1)[CH:15]=[C:14]([C:20]1[N:21]([CH:25]([CH3:27])[CH3:26])[N:22]=[CH:23][N:24]=1)[N:13]=4)[CH2:51]2)=[O:46])([CH3:43])([CH3:41])[CH3:42]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 226480948-Boc-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-3-eneHCID 582047108-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 582044623-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl esterYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

A vessel was charged with 8-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (237 mg, 0.56 mmol), PdCl2dppf.DCM (46 mg, 0.06 mmol, 10 mol %) and cesium carbonate (456 mg, 1.40 mmol) before being evacuated and refilled with nitrogen. To the resultant mixture was added a solution of 3-trifluoromethanesulfonyloxy-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester (402 mg, 0.56 mmol) in DME (2 mL), followed by water (0.2 mL). The reaction was evacuated and refilled with nitrogen before being stirred at 110° C. for 1.5 h. The reaction mixture was partitioned between ethyl acetate and water, the organic phase was separated, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-100% ethyl acetate in cyclohexane) to give 3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester as a colourless oil (177 mg, 0.35 mmol, 63%). LCMS RT=4.84 min, [M+H]+=503

Workup

  1. additionrefilled with nitrogen
  2. customThe reaction was evacuated
  3. additionrefilled with nitrogen
  4. customThe reaction mixture was partitioned between ethyl acetate and water
  5. customthe organic phase was separated
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0ec3a187aa8e4f87a998e0648c6f705a
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

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