9-Fluorenylmethyl chloroformate → 3-([(9H-Fluoren-9-ylmethoxy)carbonyl]amino)-2,2-dimethyl-3-phenylpropanoic acid

HRID 361745Notes

Reaction equation

HRID 361745 reaction equation
Cl.[C:2]1([CH:8]([C:10]([CH3:15])([CH3:14])[C:11]([OH:13])=[O:12])[NH2:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16](Cl)([O:18][CH2:19][CH:20]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]2[C:21]1=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17]>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>[C:16]([NH:9][CH:8]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:10]([CH3:15])([CH3:14])[C:11]([OH:13])=[O:12])([O:18][CH2:19][CH:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27]2[C:32]1=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:17]

Participants

5

Reactant 2

HCID 343679-Fluorenylmethyl chloroformateHCID 701996103-Amino-2,2-dimethyl-3-phenylpropanoic acid hydrochloride

Product 1

HCID 1216045063-([(9H-Fluoren-9-ylmethoxy)carbonyl]amino)-2,2-dimethyl-3-phenylpropanoic acidYield 27%

Reagents, catalysts & solvents 2

HCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Procedure

The obtained β-phenyl-α,α-dimethyl-β-alanine hydrochloride (2.0 g, 10.8 mmol) was dissolved in a 10% aqueous solution of sodium carbonate (46 ml). To the resulting solution, a solution of Fmoc-Cl (3.35 g, 12.96 mmol) in dioxane (20 ml) was added dropwise under cooling with ice and the mixture was stirred at room temperature overnight. The solvents were distilled off and the residue was dissolved in water and washed with ether. The aqueous layer was adjusted to pH 3 with concentrated HCl under cooling with ice and extracted with ethyl acetate. The collected ethyl acetate layer was washed with a saturated solution of NaCl and dried over anhydrous sodium sulfate. The solvent was distilled off and the obtained oil was applied to a silica gel column (2.5×40 cm) and eluted with a mixed solution (chloroform:methanol=50:1). The desired fractions were collected and the solvents were distilled off to yield a crystal of N-Fmoc-β-phenyl-α,α-dimethyl-β-alanine (1.21 g, 26.6%).

Workup

  1. temperatureunder cooling with ice
  2. distillationThe solvents were distilled off
  3. dissolutionthe residue was dissolved in water
  4. washwashed with ether
  5. temperatureunder cooling with ice
  6. extractionextracted with ethyl acetate
  7. washThe collected ethyl acetate layer was washed with a saturated solution of NaCl
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationThe solvent was distilled off
  10. washeluted with a mixed solution (chloroform:methanol=50:1)
  11. customThe desired fractions were collected
  12. distillationthe solvents were distilled off

Sources & evidence

ORD record
ord-81a055c1d77e473fa1692323d66ae5c0
Source dataset
uspto-grants-1999_02
Patent number
US05866592

Reaction notes

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