HCID 54333393, compound → HCID 68838832, compound

HRID 2103939Notes

Reaction equation

HRID 2103939 reaction equation
[CH2:1]([O:4][C:5]([NH:7][C@H:8]([C:17]([OH:19])=[O:18])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)=[O:6])[CH:2]=[CH2:3]>CN(C=O)C>[CH2:1]([O:4][C:5]([NH:7][C@H:8]([C:17]([OH:19])=[O:18])[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([O:16][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:14][CH:15]=1)=[O:6])[CH:2]=[CH2:3]

Participants

3

Reactant 1

HCID 54333393HCID 54333393, compound

Product 1

HCID 68838832HCID 68838832, compoundYield 126.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Alloc-Tyr-OH (38, 5.5 g) was dissolved in DMF (40 mL) and half the volume of DMF was removed under reduced pressure. The residue was cooled at 0° C. under a N2 atmosphere and sodium hydride (60% disperse, 1.9 g) was added in small portions. The suspension was stirred for one hour at 0° C. Then benzyl bromide (1.88 mL) in DMF (5 mL) was added. After one hour at RT 2N hydrochloric acid (7 mL) was added and the mixture concentrated under reduced pressure. To the residue H2O (50 mL) was added, the pH was adjusted to nine using 2N aq. sodium hydroxide and washed with a mixture of toluene and EtOAc. EtOAc was added and the mixture acidified to pH 3 using 2N hydrochloric acid. The organic layer was separated, dried (Na2SO4) and concentrated. The residue was purified using silica gel column chromatography (DCM/MeOH/AcOH, 89/10/1, v/v/v). The product from the column was dissolved in EtOAc, washed with H2O, dried (Na2SO4) and concentrated to give compound 39 (4.66 g, 77%). Rf 0.5 (DCM/MeOH/AcOH, 89/10/1, v/v/v).

Workup

  1. customhalf the volume of DMF was removed under reduced pressure
  2. additionsodium hydride (60% disperse, 1.9 g) was added in small portions
  3. additionThen benzyl bromide (1.88 mL) in DMF (5 mL) was added
  4. additionAfter one hour at RT 2N hydrochloric acid (7 mL) was added
  5. concentrationthe mixture concentrated under reduced pressure
  6. additionTo the residue H2O (50 mL) was added
  7. washwashed with a mixture of toluene and EtOAc
  8. additionEtOAc was added
  9. customThe organic layer was separated
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe residue was purified
  13. dissolutionThe product from the column was dissolved in EtOAc
  14. washwashed with H2O
  15. dry with materialdried (Na2SO4)
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-b04fb2c832434c2fab0ca3e3c07d6661
Source dataset
uspto-grants-2009_08
Patent number
US07576071B2

Reaction notes

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