Diethyl Ether → Benzylurea

HRID 1586384Notes

Reaction equation

HRID 1586384 reaction equation
S(OC[C@H](CC1C=CC=CC=1)[NH:8][C:9]([O:11]CC1C=CC=CC=1)=O)(=O)(=O)C.[Li+].CC([N-:30]C(C)C)C.[CH2:34](Br)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.CCOCC>C1COCC1.C(Cl)Cl>[CH2:34]([NH:30][C:9]([NH2:8])=[O:11])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 7498Benzyl BromideHCID 2724682Lithium diisopropylamideHCID 54080588HCID 54080588, compound

Product 1

HCID 10853BenzylureaYield 48%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Silyl lactam 1 was dissolved in dry THF (6 mL) and cooled to -78° C. To this solution was then added LDA and the reaction was stirred for 30 minutes at -78° C. after which time benzyl bromide was added via syringe. The reaction was stirred at -78° C. until reaction was complete (1.5 hours, TLC (1:9, ether:CH2Cl2) Rf (st mat.)=0.29. Rf(silyl-prod)=0.62. Rf(BzBr)=0.79). The reaction was then quenched at -78° C. with 6 uL water and then TBAF (1M in THF was added and the reaction was warmed to room temperature and stirred for 3 hours (TLC (1:9, ether:CH2Cl2) Rf(prod)=0.28). The reaction was partition betweem H2O/EtOAc and the organic layer was washed with with water and brine, dried (MgSO4) and filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (10% ether/CH2Cl2) to yield benzyl product 2 (71 mg, 48%).

Workup

  1. additionwas added via syringe
  2. customThe reaction was then quenched at -78° C. with 6 uL water
  3. additionTBAF (1M in THF was added
  4. temperaturethe reaction was warmed to room temperature
  5. stirringstirred for 3 hours (TLC (1:9, ether:CH2Cl2) Rf(prod)=0.28)
  6. customThe reaction was partition betweem H2O/EtOAc
  7. washthe organic layer was washed with with water and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel chromatography (10% ether/CH2Cl2)

Sources & evidence

ORD record
ord-8e26a77c6b3d4aa7a5660f9f6827d6f1
Source dataset
uspto-grants-1999_08
Patent number
US05945413

Reaction notes

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