L-Tyrosine → (S)-2-Amino-3-(3-((2-aminothiazol-5-yl)methyl)-4-hydroxyphenyl)propanoic acid

HRID 1755454Notes

Reaction equation

HRID 1755454 reaction equation
[NH2:1][C:2]1[S:3][C:4]([CH2:7]O)=[CH:5][N:6]=1.[NH2:9][C@H:10]([C:19]([OH:21])=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1.FC(F)(F)S(O)(=O)=O>[N+](C)([O-])=O>[NH2:9][C@@H:10]([CH2:11][C:12]1[CH:13]=[CH:14][C:15]([OH:18])=[C:16]([CH2:7][C:4]2[S:3][C:2]([NH2:1])=[N:6][CH:5]=2)[CH:17]=1)[C:19]([OH:21])=[O:20]

Participants

5

Reactant 3

HCID 6057L-TyrosineHCID 62406Trifluoromethanesulfonic acidHCID 11217273(2-Aminothiazol-5-yl)methanol

Product 1

HCID 86700104(S)-2-Amino-3-(3-((2-aminothiazol-5-yl)methyl)-4-hydroxyphenyl)propanoic acidYield 61.7%

Reagents, catalysts & solvents 1

HCID 6375NitromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of (2-aminothiazol-5-yl)methanol (35 mg, 0.269 mmol) and L-Tyrosine (199.6 mg, 1.102 mmol) in nitromethane (3.00 mL) is added trifluoromethanesulfonic acid (170 μL, 1.914 mmol). The resulting solution is sonicated for 15 sec, then heated at 80° C. for 18 h. The reaction is evaporated to dryness and the residue is purified by preparative HPLC (Condition A) using a PHENOMENEX® Luna Axia 30×100 mm S10 column from 0% Solvent B to 60% Solvent B over 12 min, ret. T=5.14 min. The product fractions are poured thru a washed WATERS OASIS® MCX 20 cc (1 g) LP extraction cartridge and washed with additional MeOH (50 mL). Elution with Aldrich 2.0M NH3/MeOH (20 mL) followed by evaporation gives 48.7 mg (55.6%) of the title compound as a light tan solid. LC/MS (Condition A): ret. T=0.63 min, (M+H)+ 294.05. Analytical HPLC: (Condition C): >95%, ret. T=3.26 min, (Condition D): >90%, ret. T=3.00 min. 1H NMR (500 MHz, DMSO-d6+D2O) δ ppm 6.86-7.04 (2 H, m), 6.67-6.76 (1 H, m), 6.58-6.67 (1 H, m), 3.74 (2 H, br. s.), 3.33 (1 H, br. s.), 3.02 (1 H, d, f=10.07 Hz), 2.68 (1 H, br. s.).

Workup

  1. customThe resulting solution is sonicated for 15 sec
  2. customThe reaction is evaporated to dryness
  3. customthe residue is purified by preparative HPLC (Condition A)
  4. customover 12 min
  5. customT=5.14 min
  6. additionThe product fractions are poured thru
  7. extractiona washed WATERS OASIS® MCX 20 cc (1 g) LP extraction cartridge
  8. washwashed with additional MeOH (50 mL)
  9. washElution with Aldrich 2.0M NH3/MeOH (20 mL)
  10. customfollowed by evaporation

Sources & evidence

ORD record
ord-f925647a03484bdaa4bd6d74ff781485
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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