Methyl iodide → N-Boc-N-methyl-3-(biphenyl-4-yl)-D-alanine

HRID 1601959Notes

Reaction equation

HRID 1601959 reaction equation
[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([CH2:7][CH:8]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:9]([OH:11])=[O:10])=[CH:3][CH:2]=1.IC.[H-].[Na+].[C:30](OCC)(=O)C>O1CCCC1.O>[C:1]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([N:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH3:30])[C:9]([OH:11])=[O:10])=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 46239082-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-phenylphenyl)propanoic Acid

Product 1

HCID 20694694N-Boc-N-methyl-3-(biphenyl-4-yl)-D-alanine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-(1,1'-Biphenyl-4-yl)-2-tert-butoxycarbonylaminopropionic acid (5.0 g; 14.66 mmol) was dissolved in dry tetrahydrofuran (45 mL). Iodomethane (7.3 mL; 117.3 mmol) was added and the reaction mixture was cooled to 0° C. Sodium hydride (1.75 g; 44.0 mmol) was added and the reaction mixture was stirred for 5 days at room temperature. Ethyl acetate (50 mL) was added and water (20 mL) was added dropwise. The solvent was removed in vacuo and the residue was dissolved in an aqueous solution of sodium hydrogen carbonate (saturated; 50 mL) and washed with diethyl ether (30 mL). The aqueous phase was acidified to pH 3 using citric acid (5%) and extracted with ethyl acetate (3×50 mL). The organic phase was washed with an aqueous solution of sodium thiosulfate (5%; 75 mL) and dried (magnesium sulfate). The solvent was removed in vacuo to afford 3.85 g of (2R)-3-(1,1'-biphenyl-4-yl)-2-(N-tert-butoxycarbonyl-N-methylamino)propionic acid.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in an aqueous solution of sodium hydrogen carbonate (saturated; 50 mL)
  3. washwashed with diethyl ether (30 mL)
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. washThe organic phase was washed with an aqueous solution of sodium thiosulfate (5%; 75 mL)
  6. dry with materialdried (magnesium sulfate)
  7. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-6b41ce029e0845e79014f7b5cd46062c
Source dataset
uspto-grants-1999_11
Patent number
US05977178

Reaction notes

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