(+-)-Penicillamine → 2-Amino-3-methyl-3-((2,4,6-trimethoxyphenyl)methylthio)butanoic acid

HRID 1883643Notes

Reaction equation

[NH2:1][CH:2]([C:6]([CH3:9])([SH:8])[CH3:7])[C:3]([OH:5])=[O:4].FC(F)(F)C(O)=O.[CH3:17][O:18][C:19]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([O:29][CH3:30])[C:20]=1[CH2:21]O>C(Cl)Cl>[NH2:1][CH:2]([C:6]([CH3:9])([S:8][CH2:21][C:20]1[C:23]([O:29][CH3:30])=[CH:24][C:25]([O:27][CH3:28])=[CH:26][C:19]=1[O:18][CH3:17])[CH3:7])[C:3]([OH:5])=[O:4]

Participants

Conditions

Temperature: 0 °C

Procedure

A suspension of 2-amino-3-methyl-3-sulfanylbutanoic acid (D-penicillamine) (5.0 g, 34 mmol) in CH2Cl2 (150 mL) was cooled to 0° C. Trifluoroacetic acid (54 mL, 703 mmol) was added dropwise over a period of 5 minutes. Then 2,4,6-trimethoxybenzyl alcohol (6.64 g, 34 mmol) in CH2Cl2 (137 mL) was added dropwise at 0° C. with stirring. Stirring was continued for 1 hour at 0° C. and 2 hours at room temperature. The solvent was removed in vacuo and the residue was dried under high vacuum for 3 hours. The crude red solid was recrystallized from 1:1:1 CH2Cl2/MeOH/EtOAc to give the title compound as a white solid (10.5 g, 95%). 1H NMR (300 MHz, CDCl3) δ6.10 (s, 2H), 3.84 (s, 6H), 3.76 (s, 3H), 3.40-4.10 (m, 3H), 1.69 (s, 3H), 1.23 (s, 3H). LRMS (EI) m/z 330 (MH+).

Workup

stirringStirring
customThe solvent was removed in vacuo
customthe residue was dried under high vacuum for 3 hours
customThe crude red solid was recrystallized from 1:1:1 CH2Cl2/MeOH/EtOAc

Sources & evidence

ORD record: ord-f182842bd18d48e9b2c89e9b0689e8e9
Source dataset: uspto-grants-2004_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06762202B2

Reaction notes

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