Hydrochloric Acid → Fmoc-l-tyr(3-tbu)-oh

HRID 1383712Notes

Reaction equation

HRID 1383712 reaction equation
[NH2:1][C@H:2]([C:15]([O:17]C)=[O:16])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=1.[OH-].[Na+].[C:21](ON1C(=O)CCC1=O)([O:23][CH2:24][CH:25]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22].C(=O)([O-])O.[Na+].Cl>CO.O1CCOCC1>[NH:1]([C:21]([O:23][CH2:24][CH:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:32]2[C:37]1=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:22])[C@H:2]([C:15]([OH:17])=[O:16])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[C:6]([C:11]([CH3:12])([CH3:13])[CH3:14])[CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 15549498Tyr(3-tBu)-OMe

Product 1

HCID 51340586Fmoc-l-tyr(3-tbu)-ohYield 61%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2.0 g (8.0 mmol) of Tyr(3-tBu)-OMe in 40 ml of methanol, 8.8 ml (8.8 mmol) of 1 N aqueous sodium hydroxide was added dropwise under cooling with ice and the mixture was stirred for 2 hours, followed by stirring at room temperature for additional 4 hours. The reaction mixture was concentrated under reduced pressure and 1 N HCl was added under cooling with ice for pH adjustment to 9; to the reaction being maintained at pH 8-9, a solution of 3.0 g (8.8 mmol) of Fmoc-OSu in 1,4-dioxane (40 ml) and a saturated aqueous solution of sodium hydrogencarbonate were alternately added dropwise and the mixture was stirred at room temperature for 1 day. After being rendered acidic with hydrochloric acid, the reaction mixture was extracted with ethyl acetate and the ethyl acetate layer was dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting crude product was subjected to silica gel column chromatography (eluting solvents were ethyl acetate:n-hexane=1:1 and acetic acid supplemented ethyl acetate:n-hexane=1:1); to remove the acetic acid used in eluting, the fractions were washed with water, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to give Fmoc-Tyr(3-tBu)-OH in the amount of 2.3 g (yield: 61%).

Workup

  1. temperatureunder cooling with ice
  2. stirringby stirring at room temperature for additional 4 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure and 1 N HCl
  4. additionwas added
  5. temperatureunder cooling with ice for pH adjustment to 9
  6. temperatureto the reaction being maintained at pH 8-9
  7. stirringthe mixture was stirred at room temperature for 1 day
  8. extractionthe reaction mixture was extracted with ethyl acetate
  9. dry with materialthe ethyl acetate layer was dried with anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. washThe resulting crude product was subjected to silica gel column chromatography (eluting solvents were ethyl acetate:n-hexane=1:1 and acetic acid supplemented ethyl acetate:n-hexane=1:1)
  12. customto remove the acetic acid
  13. washin eluting
  14. washthe fractions were washed with water
  15. dry with materialdried with anhydrous magnesium sulfate
  16. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0e02d6006ec24c6f870256da2d764716
Source dataset
uspto-grants-2001_07
Patent number
US06255285B1

Reaction notes

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