Pyridine → N-(Cyclohexanecarbonyl)-L-tyrosine

HRID 397247Notes

Reaction equation

HRID 397247 reaction equation
[CH:1]1([C:7](Cl)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.C([O:23][C:24](=[O:42])[C@H:25]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34]CC2C=CC=CC=2)=[CH:30][CH:29]=1)[NH2:26])C1C=CC=CC=1>CO.O1CCCC1.[Pd]>[CH:1]1([C:7]([NH:26][C@H:25]([C:24]([OH:42])=[O:23])[CH2:27][C:28]2[CH:29]=[CH:30][C:31]([OH:34])=[CH:32][CH:33]=2)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 1049PyridineHCID 75938Cyclohexanecarbonyl chlorideHCID 7408223(S)-Benzyl 2-amino-3-(4-(benzyloxy)phenyl)propanoate

Product 1

HCID 15432050N-(Cyclohexanecarbonyl)-L-tyrosineYield 64%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Cyclohexanoyl chloride (7 mL, 47 mmole) was added dropwise to a stirred solution of dry pyridine (400 mL) and O-benzyltyrosine benzyl ester (25 g, 46.8 mmole). The reaction temperature was maintained at 0° C. throughout the addition. The reaction mixture was stirred for an additional 2 hours after the addition was complete. The reaction mixture was concentrated to dryness in vacuo to provide a solid material. The solid was washed with aqueous hydrochloric acid (1N, 4×400 mL). The residue was dissolved in ethyl acetate (300 mL), washed with aqueous hydrochloric acid (1N, 2×500 mL), aqueous sodium bicarbonate (2×300 mL), and dried over magnesium sulfate. Filtration, followed by concentration in vacuo, provided an oil which was dissolved in methanol/tetrahydrofuran (400 mL/70 mL) and was hydrogenated at atmospheric pressure and room temperature over 10% palladium on carbon (600 mg). The reaction mixture was filtered through Celite and concentrated in vacuo to provide a solid which was recrystallized from ethyl acetate/hexane. The crystals were collected to-provide the N-cyclohexanoyl-(L)-tyrosine (8.7 g, 64%) as a white solid.

Workup

  1. additionafter the addition
  2. concentrationThe reaction mixture was concentrated to dryness in vacuo
  3. customto provide a solid material
  4. washThe solid was washed with aqueous hydrochloric acid (1N, 4×400 mL)
  5. dissolutionThe residue was dissolved in ethyl acetate (300 mL)
  6. washwashed with aqueous hydrochloric acid (1N, 2×500 mL), aqueous sodium bicarbonate (2×300 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationFiltration
  9. concentrationfollowed by concentration in vacuo
  10. customprovided an oil which
  11. filtrationThe reaction mixture was filtered through Celite
  12. concentrationconcentrated in vacuo
  13. customto provide a solid which
  14. customwas recrystallized from ethyl acetate/hexane
  15. customThe crystals were collected

Sources & evidence

ORD record
ord-3f5029d46d5645a6b1a91e1c84a9d7a1
Source dataset
uspto-grants-2003_08
Patent number
US06610329B2

Reaction notes

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