Potassium Hydroxide → HCID 117857614, compound

HRID 1483162Notes

Reaction equation

HRID 1483162 reaction equation
[CH:1]1([CH2:5][N:6]2[CH2:15][CH2:14][C@@:13]34[C:16]5[C:22]6[CH2:23][C@@H:7]2[C@@H:8]3[CH2:9][CH2:10][C:11](=[O:26])[C@@H:12]4[O:18][C:17]=5[C:19]([C:24]#[N:25])=[CH:20][CH:21]=6)[CH2:4][CH2:3][CH2:2]1.[OH-:27].[K+]>C(O)(C)(C)C>[CH:1]1([CH2:5][N:6]2[CH2:15][CH2:14][C@@:13]34[C:16]5[C:22]6[CH2:23][C@@H:7]2[C@@H:8]3[CH2:9][CH2:10][C:11](=[O:26])[C@@H:12]4[O:18][C:17]=5[C:19]([C:24]([NH2:25])=[O:27])=[CH:20][CH:21]=6)[CH2:2][CH2:3][CH2:4]1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 117857410HCID 117857410, compound

Product 1

HCID 117857614HCID 117857614, compoundYield 104.4%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (4R,4aR,7aR,12bS)-3-(cyclobutylmethyl)-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-9-carbonitrile (24 g, 68.9 mmol) in tert-butanol (240 mL) was added KOH (2.1 g, 37.1 mmol). The reaction was heated to 100° C. for 15 minutes. The reaction was allowed to cool to room temperature and concentrated to 50% volume. Diluted with water and extracted with ethyl acetate twice. The organic phases were combined, washed with to sodium hydrogen carbonate solution and brine and dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica chromatography eluted with 4% methanol in dichloromethane to give to give (4R,4aR,7aR,12bS)-3-(cyclobutylmethyl)-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-9-carboxamide (14.2 g, 89% pure LCMS, 56% yield); [M+H]+ 367.2.

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated to 50% volume
  3. additionDiluted with water
  4. extractionextracted with ethyl acetate twice
  5. washwashed with to sodium hydrogen carbonate solution and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica chromatography
  9. washeluted with 4% methanol in dichloromethane
  10. customto give

Sources & evidence

ORD record
ord-b763e2d1005a4c3e8ac2420483a99099
Source dataset
uspto-grants-2016_08
Patent number
US09416137B2

Reaction notes

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