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

HRID 1371280Notes

Reaction equation

HRID 1371280 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-0a8b48ec8fc44d99855d033ebf1ba7f7
Source dataset
uspto-grants-2007_01
Patent number
US07157430B2

Reaction notes

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