Dimethyl Sulfate → (2S)-2-[(tert-Butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propionic acid methyl ester

HRID 23220Notes

Reaction equation

HRID 23220 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O.[OH-].[NH4+]>CN(C=O)C>[CH3:22][O:11][C:10](=[O:12])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][C:14]1[CH:15]=[C:16]([F:21])[CH:17]=[C:18]([F:20])[CH:19]=1

Participants

6

Reactant 4

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 27790093,5-Difluoro-L-phenylalanine, N-BOC protected

Product 1

HCID 9836527(2S)-2-[(tert-Butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid (I, 5.0 g, 0.017 moles, 1.0 equivalent) and potassium carbonate (2.5 g, 0.018 moles, 1.1 equivalent) and DMF (100 mL) are mixed. To this heterogeneous mixture is then added dimethyl sulfate (1.6 mL, 2.1 g, 0.017 moles, 1.0 equivalent) and the contents are then stirred at 20-25° overnight. Once the reaction is complete as measured by HPLC, ammonium hydroxide (10%, 20 mL) is added and allowed to stir for 1 hr. The contents are stirred for 30 min then cooled to 0° and filtered. The solids are washed with cold water (20 mL) and dried under reduced pressure to give the title compound.

Workup

  1. additionis added
  2. stirringThe contents are stirred for 30 min
  3. temperaturethen cooled to 0°
  4. filtrationfiltered
  5. washThe solids are washed with cold water (20 mL)
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-354a384970404fd4a9fa75e912c9f753
Source dataset
uspto-grants-2005_02
Patent number
US06849750B2

Reaction notes

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