Methanol → HCID 58960095, compound

HRID 916162Notes

Reaction equation

HRID 916162 reaction equation
[CH3:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]2=O)=[O:7])=[CH:4][CH:3]=1.[CH3:17][O:18][C:19](=[O:30])[C@H:20]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)[NH2:21].O.CO>C1(OC)C=CC=CC=1.[Pd]>[CH3:17][O:18][C:19](=[O:30])[CH:20]([NH:21][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:6](=[O:7])[C:5]1[CH:15]=[CH:16][C:2]([CH3:1])=[CH:3][CH:4]=1)[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 70652Tyrosine Methyl EsterHCID 11218191HCID 11218191, compound

Product 1

HCID 58960095HCID 58960095, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 7519AnisoleSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-(4-methylbenzoyl)cyclohexanone (97.2 g, 0.45 mol), L-tyrosine methyl ester (78.0 g, 0.40 mol) in anisole (1000 ml) is added 5% palladium on carbon (20 g), then the mixture is heated to reflux for 2 h while the resulting water is removed by a Dean-Stark apparatus. The mixture is cooled to 80° C., and the Pd/C is filtered and washed with anisole (3×60 ml). The mixture is cooled to 40° C., hexane (1000 ml) is added and the mixture kept at −20° C. for 48 h. The solid is filtered and washed with hexane (5×200 ml) to yield the crude 2-[(2-(4-methyl benzoyl)phenyl)-amino]-3-(4-hydroxyphenyl)-propionic acid methyl ester. The crude product is mixed with 250 ml of methanol and is refluxed for 30 min. After cooled to 0° C., the product is filtered, washed with methanol (2×50 ml), and dried under a vacuum to give the title compound (59.1 g, 38%).

Workup

  1. temperaturethe mixture is heated
  2. customis removed by a Dean-Stark apparatus
  3. filtrationthe Pd/C is filtered
  4. washwashed with anisole (3×60 ml)
  5. temperatureThe mixture is cooled to 40° C.
  6. additionhexane (1000 ml) is added
  7. filtrationThe solid is filtered
  8. washwashed with hexane (5×200 ml)
  9. customto yield the crude 2-[(2-(4-methyl benzoyl)phenyl)-amino]-3-(4-hydroxyphenyl)-propionic acid methyl ester
  10. temperatureis refluxed for 30 min
  11. temperatureAfter cooled to 0° C.
  12. filtrationthe product is filtered
  13. washwashed with methanol (2×50 ml)
  14. customdried under a vacuum

Sources & evidence

ORD record
ord-64e0a7a984b647718f05cb33aeec5053
Source dataset
uspto-grants-2007_09
Patent number
US07268157B2

Reaction notes

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