Ethyl Acetate → N-(tert-Butoxycarbonyl)-O-(4-formylphenyl)-L-tyrosine

HRID 2111868Notes

Reaction equation

HRID 2111868 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].F[C:28]1[CH:35]=[CH:34][C:31]([CH:32]=[O:33])=[CH:30][CH:29]=1.C(OCC)(=O)C>CN(C=O)C.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][C:28]2[CH:35]=[CH:34][C:31]([CH:32]=[O:33])=[CH:30][CH:29]=2)=[CH:15][CH:16]=1)[C:18]([OH:20])=[O:19])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 680234-FluorobenzaldehydeHCID 117439L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-

Product 1

HCID 59751099N-(tert-Butoxycarbonyl)-O-(4-formylphenyl)-L-tyrosine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Dissolve N-tert-butoxycarbonyl-L-tyrosine (2.42 Kg, 8.3 moles) in dry DMF (7.26 L) under argon and still till complete dissolution. Add K2CO3 (3.57 Kg, 25.81 moles), 4-fluorobenzaldeyde (5.34 Kg, 43.01 moles) and stir at 70±5° C. for 48 h under argon. Cool the reaction mixture less than 30° C. Poured the reaction mixture in water (75 L) and stir for 15 min. Add ethyl acetate (40 L) and stir for 30 min. Separate the organic layer and aqueous layer was acidified with HCl (6M) to pH 2. Solid precipitated was dissolved in ethyl acetate (40 L) and aqueous layer was separated. Organic layer was washed with brine (40 L), dried on sodium sulfate and evaporate solvent under reduced pressure. Observed HPLC purity (93.4%) and chiral purity by HPLC (100%). Dry with anhydrous MgSO4 and evaporate under reduced pressure. Pale yellow solid (3.06 Kg, 99.3%). 1H NMR (300 MHz, DMSO-d6): 9.89 (s, 1H), 7.82 (d, J=8.4 Hz, 2H), 7.23 (d, J=8.4 Hz, 2H), 7.00 (overlapped d, J=9.0 Hz, 4H), 4.63 (m, 1H), 3.2 (m, 1H), 3.06 (m, 1H), 1.40 (s, 9H).

Workup

  1. dissolutionstill till complete dissolution
  2. temperatureCool the reaction mixture less than 30° C
  3. customSeparate the organic layer and aqueous layer
  4. customSolid precipitated
  5. dissolutionwas dissolved in ethyl acetate (40 L)
  6. customaqueous layer was separated
  7. washOrganic layer was washed with brine (40 L)
  8. customdried on sodium sulfate
  9. customevaporate solvent under reduced pressure
  10. dry with materialDry with anhydrous MgSO4
  11. customevaporate under reduced pressure

Sources & evidence

ORD record
ord-b89379200cb446dca1731afabc39722d
Source dataset
uspto-grants-2009_04
Patent number
US07521465B2

Reaction notes

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