Water → N-(2-benzoylphenyl)tyrosine methyl ester

HRID 1597442Notes

Reaction equation

[C:1]([CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C:10]1=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][O:17][C:18](=[O:29])[C@H:19]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1)[NH2:20].O>[Pd].C1(OC)C=CC=CC=1>[CH3:16][O:17][C:18](=[O:29])[C@@H:19]([NH:20][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:1](=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A stirred mixture of 92 g (0.45 mol) 2-benzoyl-cyclohexanone, (Denny, W. A. et. al. J. Med. Chem. 1978, 21(5), 430-7) 78 g (0.40 mol) L-Tyrosine methyl ester, 17.0 g Palladium on activated carbon (10%) was refluxed for 2 h in 1 L anisole while the resulting water was removed by a Dean-Stark apparatus. The mixture was cooled to 80° C. and the Pd/C was filtered, and washed with 50 mL anisole three times. The mixture was cooled to 40° C., 1 L hexane was added and kept at −20° C. for 48 h. The solid was filtered, washed with 200 mL hexane five times to yield 89.0 g crude (S)-2-(2-Benzoyl-phenylamino)-3-(4-hydroxy-phenyl)-propionic acid methyl ester. This solid was mixed with 220 mL of MeOH, and the slurry was refluxed for 30 min. The mixture was cooled to 0° C., the product was filtered and washed with 50 mL cold (−20° C.) MeOH twice, then dried under reduced pressure to yield 67.4 g the of the title compound. mp 185-6° C.; low resolution MS (ESP+) m/e 376 (MH+).

Workup

customwas removed by a Dean-Stark apparatus
filtrationthe Pd/C was filtered
washwashed with 50 mL anisole three times
temperatureThe mixture was cooled to 40° C.
addition1 L hexane was added
filtrationThe solid was filtered
washwashed with 200 mL hexane five times

Sources & evidence

ORD record: ord-00f9663f611e401dbb4c91b24659215f
Source dataset: uspto-grants-2001_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06294580B1

Reaction notes

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