2-(6-Methoxy-2-naphthyl)propionic acid → HCID 18973230, compound

HRID 975179

Reaction equation

HRID 975179 reaction equation
[CH3:1][NH:2][CH2:3][C@H:4]([OH:13])[C:5]1[CH:6]=[CH:7][C:8]([OH:12])=[C:9]([OH:11])[CH:10]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:37][O:38][C:39]1[CH:40]=[C:41]2[C:46](=[CH:47][CH:48]=1)[CH:45]=[C:44]([CH:49]([CH3:53])[C:50]([OH:52])=O)[CH:43]=[CH:42]2>C(#N)C>[OH:11][C:9]1[CH:10]=[C:5]([CH:4]([OH:13])[CH2:3][N:2]([CH3:1])[C:50](=[O:52])[CH:49]([C:44]2[CH:43]=[CH:42][C:41]3[C:46](=[CH:47][CH:48]=[C:39]([O:38][CH3:37])[CH:40]=3)[CH:45]=2)[CH3:53])[CH:6]=[CH:7][C:8]=1[OH:12]

Participants

6

Reactant 4

HCID 13022-(6-Methoxy-2-naphthyl)propionic acidHCID 5816EpinephrineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 18973230HCID 18973230, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Epinephrine (Aldrich, 3.18 grams [g], 17.3 millimoles [mmol]), 1-hydroxylbenzotriazole hydrate (Aldrich, 1.76 g, 12.9 mmol) and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide HCl (Aldrich, 2.49 g, 12.9 mmol) were added to acetonitrile (200 milliliters [ml]). After stirring for 10 minutes, a solution of 6-methoxy-α-methyl-2-naphthaleneacetic acid (Aldrich, 2.0 g, 8.66 mmol), in 50 ml of acetonitrile, was added dropwise. After stirring for 16 hours, the reaction mixture was concentrated in vacuo (under reduced pressure), and the residue was partitioned between water (100 ml) and methylene chloride (100 ml). The layers were separated and the aqueous layer was extracted with methylene chloride (2×50 ml) and ethyl acetate (50 ml). The combined organic extracts were treated with methanol until a clear solution was formed. This solution was dried (magnesium sulfate) and concentrated in vacuo. Flash chromatography of the residue (silica gel, 95:5, volume:volume [v:v], methylene chloride:methanol), and concentration of the appropriate fractions resulted in the formation of a solid. The solid was recrystallized from a mixture of ethyl acetate and hexane to give N-(2(3,4-dihydroxyphenyl)-2-hydroxyethyl)-N-methyl-2-(6-methoxy-2-naphthyl)propionamide, a mixture of diastereomers, as a white solid (0.95 g, 27% yield).

Workup

  1. stirringAfter stirring for 16 hours
  2. concentrationthe reaction mixture was concentrated in vacuo (under reduced pressure)
  3. customthe residue was partitioned between water (100 ml) and methylene chloride (100 ml)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with methylene chloride (2×50 ml) and ethyl acetate (50 ml)
  6. additionThe combined organic extracts were treated with methanol until a clear solution
  7. customwas formed
  8. dry with materialThis solution was dried (magnesium sulfate)
  9. concentrationconcentrated in vacuo
  10. customFlash chromatography of the residue (silica gel, 95:5, volume:volume [v:v], methylene chloride:methanol), and concentration of the appropriate fractions resulted in the formation of a solid
  11. customThe solid was recrystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-225cc72976a048ff9a2f99ac99079e35
Source dataset
uspto-grants-1997_03
Patent number
US05607966

Linked notes

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