1-Hydroxy-2-naphthoic acid → 2-[(1-Hydroxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid methyl ester

HRID 1889259Notes

Reaction equation

HRID 1889259 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:12]([OH:14])=O.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C.C(N(CC)C(C)C)(C)C.Cl.[NH2:44][C:45]([CH3:51])([CH3:50])[C:46]([O:48][CH3:49])=[O:47]>CN(C=O)C>[CH3:49][O:48][C:46](=[O:47])[C:45]([NH:44][C:12]([C:3]1[CH:4]=[CH:5][C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]=1[OH:1])=[O:14])([CH3:51])[CH3:50]

Participants

7

Reactant 5

HCID 68441-Hydroxy-2-naphthoic acidHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 13258034Methyl 2-aminoisobutyrate hydrochloride

Product 1

HCID 667009722-[(1-Hydroxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid methyl esterYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4.70 g 1-hydroxy-2-naphthalene carboxylic acid in 40 ml abs. DMF under inert atmosphere 3.72 g 1-hydroxybenzotriazole, 8.89 g N,N′-diisopropyl carbodiimide and 7 ml of N,N-diisopropylethylamine were added at 0° C. After 30 minutes at 0° C. 4.22 g of methyl 2-aminoisobutyrate hydrochloride, followed by 5 ml of N,N-diisopropylethylamine were added. After 16 h at room temperature the reaction mixture was concentrated, the residue was taken up in ethyl acetate and washed with 2 M HCl and brine. The organic layer was dried over magnesium sulphate, concentrated and the resulting residue was crystallized from toluene to yield 4.18 g of 2-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid methyl ester.

Workup

  1. additionwere added
  2. concentrationAfter 16 h at room temperature the reaction mixture was concentrated
  3. washwashed with 2 M HCl and brine
  4. dry with materialThe organic layer was dried over magnesium sulphate
  5. concentrationconcentrated
  6. customthe resulting residue was crystallized from toluene

Sources & evidence

ORD record
ord-9bcdfad294ff469eac993aff5a6423f0
Source dataset
uspto-grants-2013_08
Patent number
US08501981B2

Reaction notes

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