Naphthoxyacetic acid → (3S)-3-[N-((1-Naphthyloxy)Acetyl)Leucinyl]Amino-4-Oxobutanoic Acid tert-Butyl Ester Semicarbazone

HRID 1066036Notes

Reaction equation

HRID 1066036 reaction equation
[C:1]1([O:11][CH2:12][C:13]([OH:15])=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[C:16]([O:20][C:21](=[N:35][NH:36][C:37]([NH2:39])=[O:38])[CH2:22][C@H:23]([NH:26][C:27](=[O:34])[C@H:28]([CH2:30][CH:31]([CH3:33])[CH3:32])[NH2:29])[CH:24]=[O:25])([CH3:19])([CH3:18])[CH3:17].O.OC1C2N=NNC=2C=CC=1.Cl.C(N=C=NC(N)CC(C)C)C>CN1CCCC1=O.C(Cl)Cl>[C:16]([O:20][C:21](=[N:35][NH:36][C:37]([NH2:39])=[O:38])[CH2:22][C@H:23]([NH:26][C:27](=[O:34])[C@H:28]([CH2:30][CH:31]([CH3:33])[CH3:32])[NH:29][C:13](=[O:15])[CH2:12][O:11][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[CH:24]=[O:25])([CH3:18])([CH3:19])[CH3:17]

Participants

7

Reactant 4

HCID 76313Naphthoxyacetic acidHCID 221346061-Ethyl-3-(3',3'-dimethyl-1'-aminopropyl)carbodiimide hydrochlorideHCID 865839973(S)-(Leucinyl)amino-4-oxobutanoic acid, t-butyl ester semicarbazoneHCID 178526939HCID 178526939, compound

Product 1

HCID 86585450(3S)-3-[N-((1-Naphthyloxy)Acetyl)Leucinyl]Amino-4-Oxobutanoic Acid tert-Butyl Ester SemicarbazoneYield 94%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (1-naphthyloxy)acetic acid (0.150 g, 0.74 mmol) and (3S)-3-(leucinyl)amino-4-oxobutanoic acid tert-butyl ester semicarbazone (0.360 g, ca 0.83 mmol) in N-methylpyrrolidone(2.0 mL)-CH2Cl2(2.0 mL) at 0° C. (ice bath) under nitrogen was added hydroxybenzotriazole hydrate (0.130 g) followed by 1-ethyl-3-(3′,3′-dimethyl-1′-aminopropyl)carbodiimide hydrochloride (0.195 g, 1.02 mmol). After stirring at 0° C. for 1 hrs and at room temperature for 5 hrs, the mixture was partitioned between EtOAc-water. The organic phase was washed with water, 5% KHSO4, saturated NaHCO3 and saturated NaCl solutions, dried over anhydrous Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatography eluting with MeOH—CH2Cl2 (2:100 then 5:100) to give the title compound (0.366 g, 94%) as a colorless foam, TLC(MeOH—CH2Cl2; 5:95) Rf=0.20.

Workup

  1. customthe mixture was partitioned between EtOAc-water
  2. washThe organic phase was washed with water, 5% KHSO4, saturated NaHCO3 and saturated NaCl solutions
  3. dry with materialdried over anhydrous Na2SO4
  4. customevaporated to dryness
  5. customThe crude product was purified by flash chromatography
  6. washeluting with MeOH—CH2Cl2 (2:100

Sources & evidence

ORD record
ord-19016f80ef394d62be23d691cbeee408
Source dataset
uspto-grants-2001_06
Patent number
US06242422B1

Reaction notes

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