3-Methoxy-dl-tyrosine → Tert-butyl 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoate

HRID 1889152Notes

Reaction equation

HRID 1889152 reaction equation
C(O[C:5]([CH3:8])([CH3:7])[CH3:6])(=O)C.[NH2:9][CH:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([O:22][CH3:23])[CH:16]=1)[C:11]([OH:13])=[O:12].FC(F)(F)S(O)(=O)=O.[OH-].[Na+].C([O-])([O-])=O.[K+].[K+]>[Cl-].[Na+].O.CC(=O)OCC>[NH2:9][CH:10]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([O:22][CH3:23])[CH:16]=1)[C:11]([O:13][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:12]

Participants

8

Reactant 5

HCID 16703-Methoxy-dl-tyrosineHCID 10908tert-Butyl acetateHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acid

Product 1

HCID 58545613Tert-butyl 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoateYield 37.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Prepared using General Procedure 1: To tert-butyl acetate (192 ml, 1435 mmol) was added finely ground 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoic acid (10.1 g, 47.8 mmol). The mixture was sonicated for 10 min to give a suspension. Trifluoromethanesulfonic acid (5.50 ml, 62.2 mmol) was added with stirring and the mixture was stirred overnight. The crude reaction was poured into a mixture of 2N NaOH (150 mL), brine (100 mL), ice (200 mL), and EA (100 mL) and basified to pH 9 with solid K2CO3. The mixture was filtered through celite and extracted with EA (2×100 mL). The organics were dried over MgSO4 and concentrated. The product residue was purified by chromatography (MeOH/DCM) to afford 4.75 g (37%) of tert-butyl 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoate INT-1. LCMS-ESI (m/z) calculated for C14H21NO4: 267; found 268 [M+H]+, tR=0.9 min (Method 4). 1H NMR (400 MHz, DMSO) δ 8.71 (s, 1H), 6.76-6.71 (d, J=1.9 Hz, 1H), 6.70-6.61 (m, 1H), 6.60-6.53 (m, 1H), 3.75-3.68 (s, 3H), 3.32 (s, 1H), 2.68 (m, 2H), 1.75 (s, 2H), 1.33 (s, 9H).

Workup

  1. customPrepared
  2. customThe mixture was sonicated for 10 min
  3. customto give a suspension
  4. stirringthe mixture was stirred overnight
  5. customThe crude reaction
  6. filtrationThe mixture was filtered through celite
  7. extractionextracted with EA (2×100 mL)
  8. dry with materialThe organics were dried over MgSO4
  9. concentrationconcentrated
  10. customThe product residue was purified by chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-cb35ceeaeabf45359ea6c9e34714b9b7
Source dataset
uspto-grants-2013_08
Patent number
US08501982B2

Reaction notes

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