Methanol → HCID 58960084, compound

HRID 916159Notes

Reaction equation

HRID 916159 reaction equation
[C:1]([C:5]1[CH:19]=[CH:18][C:8]([C:9]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C:12]2=O)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:20][O:21][C:22](=[O:33])[C@H:23]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1)[NH2:24].O.CO>C1(OC)C=CC=CC=1.[Pd]>[CH3:20][O:21][C:22](=[O:33])[CH:23]([NH:24][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:9](=[O:10])[C:8]1[CH:18]=[CH:19][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=1)[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 70652Tyrosine Methyl EsterHCID 67133289HCID 67133289, compound

Product 1

HCID 58960084HCID 58960084, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 7519AnisoleSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-(4-tert-butylbenzoyl)cyclohexanone (116.1 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-tert-butylbenzoyl)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 (70.7 g, 41.0%).

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-tert-butylbenzoyl)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-cd11330e0a6841fca064b88a38dceee3
Source dataset
uspto-grants-2007_09
Patent number
US07268157B2

Reaction notes

Loading…