N-Hydroxyphthalimide → HCID 21075918, compound

HRID 2355649Notes

Reaction equation

HRID 2355649 reaction equation
[OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].[CH3:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[CH:21]=[C:20]([C@H:25]([CH3:29])[C:26](O)=[O:27])[CH:19]=[CH:18]2.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CN(C=O)C>[CH3:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[CH:21]=[C:20]([C@H:25]([CH3:29])[C:26]([O:1][N:2]1[C:3](=[O:12])[C:4]3[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=3[C:6]1=[O:7])=[O:27])[CH:19]=[CH:18]2

Participants

6

Reactant 3

HCID 10665N-HydroxyphthalimideHCID 156391NaproxenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 21075918HCID 21075918, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of N-hydroxyphthalimide (7.1 g, 43.4 mmol), (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 10 g, 43.4 mmol) and N,N-dimethylaminopyridine (DMAP, 5.3 g, 43.4 mmol) in CH2Cl2 (70 mL) and DMF (30 mL) at 0° C. was treated with 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (8.3 g, 43.4 mmol) in CH2Cl2 (50 mL). The reaction mixture was stirred at room temperature for 16 hours and the solvent was evaporated under vacuum. The residue was then dissolved in EtOAc, washed with brine, dried over Na2SO4 and filtered. The residue after evaporation of the solvent was chromatographed on silica gel eluting with EtOAc:hexane (1:1) to give the title compound (7.6 g, 47% yield) as a white solid. Mp 110-112° C. 1H NMR (300 MHz, d6-DMSO) δ 7.80-8.06 (m, 7H), 7.50 (dd, J=1.7 and 8.5 Hz, 1H), 7.32-7.37 (m, 1H), 7.20 (dd, J=2.5 and 9.0 Hz, 1H), 4.50 (q, J=7.1 Hz, 1H), 3.89 (s, 3H), 1.64 (d, J=7.1 Hz, 3H). 13C NMR (75 MHz, d6-DMSO) δ 171.2, 161.8, 157.5, 153.0, 135.5, 133.6, 133.5, 129.3, 128.4, 128.2, 127.3, 126.1, 126.0, 124.0, 119.0, 105.8, 55.2, 41.8, 18.6. Mass spectrum (API-TIS) m/z 376 (MH+), 393 (MNH4+).

Workup

  1. customthe solvent was evaporated under vacuum
  2. dissolutionThe residue was then dissolved in EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe residue after evaporation of the solvent
  7. customwas chromatographed on silica gel eluting with EtOAc:hexane (1:1)

Sources & evidence

ORD record
ord-ab240868ed284f0aadbc8d6f43d7adbf
Source dataset
uspto-grants-2010_07
Patent number
US07754772B2

Reaction notes

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