Dimethyl Sulfate → N-t-butoxycarbonyl(3,5-difluorophenyl)alanine methyl ester

HRID 1062895Notes

Reaction equation

HRID 1062895 reaction equation
[C:1]([O:5][C:6]([N:8]([C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=1)[C@H:9]([C:11]([OH:13])=[O:12])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]([O-])([O-])=O.[K+].[K+].COS(OC)(=O)=O.CCCCCCC>C1COCC1.C(OCC)(=O)C>[CH3:22][O:12][C:11](=[O:13])[C@H:9]([CH3:10])[N:8]([C:14]1[CH:15]=[C:16]([F:21])[CH:17]=[C:18]([F:20])[CH:19]=1)[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 8900HeptaneHCID 11430Potassium CarbonateHCID 69735303N-t-butoxycarbonyl(3,5-difluorophenyl)alanine

Product 1

HCID 69734307N-t-butoxycarbonyl(3,5-difluorophenyl)alanine methyl esterYield 86%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-t-butoxycarbonyl(3,5-difluorophenyl)alanine (2.6 g, 8.6 mmol) in 35 mL of dry THF under nitrogen is stirred with 2.0 g (14.5 mmol) of pulverized K2CO3 and 1.0 mL (10.5 mmol) of dimethylsulfate at 40° C. for 17 h. The mixture is diluted with ethyl acetate, washed twice with 1 N KH2PO4, once with 1 N NaHCO3, twice with water, and finally with brine. The organic phase is dried with Na2SO4 and concentrated to a sticky solid. Trituration with heptane affords 2.32 g (7.4 mmol, 85%) of N-t-butoxycarbonyl(3,5-difluorophenyl)alanine methyl ester as a white solid. 1H NMR (CDCl3) δ 6.72-6.56 (m, 3H), 5.04 (d, J=8 Hz, 1H), 4.57 (q, J=6 Hz, 1H), 3.75 (s, 3H), 3.14 (dd, J=6, 14 Hz, 1H), 3.01 (dd, J=6, 14 Hz, 1H), 1.43 (s, 9H).

Workup

  1. washwashed twice with 1 N KH2PO4, once with 1 N NaHCO3, twice with water
  2. dry with materialThe organic phase is dried with Na2SO4
  3. concentrationconcentrated to a sticky solid

Sources & evidence

ORD record
ord-efa331d5f8ae41d3b1b7122fdbfea4be
Source dataset
uspto-grants-2005_11
Patent number
US06962934B2

Reaction notes

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