Lithium → HCID 9827824, compound

HRID 430814Notes

Reaction equation

HRID 430814 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([NH:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:32][CH:31]=2)[C:17]([NH:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([NH:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:32][CH:31]=2)[CH2:17][NH:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 3028194LithiumHCID 18352016HCID 18352016, compound

Product 1

HCID 9827824HCID 9827824, compoundYield 20.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 700 mg (1.36 mmol) 3-(4-benzyloxy-phenyl)-2-(4-tert-butyl-benzylamino)-N-(2-piperidin-1-yl-ethyl)-propionamide (Example 13) in 28 mL dry THF was treated portionwise with 258 mg (6.80 mmol) lithium tetrahydriodoaluminate, and the resulting suspension was heated under reflux for 24 hours. The mixture was then carefully quenched with 0.35 mL H2O and filtered, and the resulting solids were washed with THF. The filtrate was diluted with 30 mL H2O, and the THF removed under reduced pressure. The aqueous layer was extracted with three 40 mL portions of ethyl acetate. The combined organic extracts were washed with 100 mL each of saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous magnesium sulphate, and concentrated at reduced pressure to give an amber oil. The oil was purified by column chromatography on silica gel (230-400 mesh) using 20% methanol in chloroform as eluant to give 141 mg (20%) of the title compound as a viscous, pale yellow liquid.

Workup

  1. temperaturethe resulting suspension was heated
  2. temperatureunder reflux for 24 hours
  3. customThe mixture was then carefully quenched with 0.35 mL H2O
  4. filtrationfiltered
  5. washthe resulting solids were washed with THF
  6. additionThe filtrate was diluted with 30 mL H2O
  7. customthe THF removed under reduced pressure
  8. extractionThe aqueous layer was extracted with three 40 mL portions of ethyl acetate
  9. washThe combined organic extracts were washed with 100 mL each of saturated aqueous sodium bicarbonate solution and brine
  10. dry with materialdried over anhydrous magnesium sulphate
  11. concentrationconcentrated at reduced pressure
  12. customto give an amber oil
  13. customThe oil was purified by column chromatography on silica gel (230-400 mesh)

Sources & evidence

ORD record
ord-8bbb0b107d664b8581e9e1ff6475b35a
Source dataset
uspto-grants-2001_11
Patent number
US06323243B1

Reaction notes

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