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

HRID 2111868노트

반응식

HRID 2111868 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b89379200cb446dca1731afabc39722d
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07521465B2

반응 노트

불러오는 중…