Naproxen → HCID 10024094, compound

HRID 1514761Notes

Reaction equation

HRID 1514761 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:17])[C:14]([OH:16])=[O:15])[CH:7]=[CH:6]2.[N+:18]([O:21][CH:22]1[O:29][CH:28]2[CH:24]([O:25][CH2:26][C@@H:27]2O)[CH2:23]1)([O-:20])=[O:19].Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:17])[C:14]([O:16][C@@H:27]1[CH2:26][O:25][CH:24]3[CH:28]1[O:29][CH:22]([O:21][N+:18]([O-:20])=[O:19])[CH2:23]3)=[O:15])[CH:7]=[CH:6]2

Participants

5

Reactant 3

HCID 156391NaproxenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66624656HCID 66624656, compound

Product 1

HCID 10024094HCID 10024094, compoundYield 97.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 1 g, 4.43 mmol) and (2S)-7-(nitrooxy)-4,8-dioxabicyclo(3.3.0) octan-2-ol (isosorbide 5-mononitrate, 1 g, 5.21 mmol) in anhydrous dichloromethane (25 mL) were added 1-(3-(dimethylamino) propyl)-3-ethylcarbodiimide hydrochloride (EDAC, 1.17 g, 1.4 eq) and a catalytic amount of N,N-dimethylaminopyridine (DMAP) at room temperature under nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with CH2Cl2 and washed H2O, brine, dried over sodium sulfate, filtered, and the organic extracts were evaporated. The product was purified by column chromatography on silica gel eluting with EtOAc:hexane (3:7 to 1:1) to give the title compound (1.71 g, 97.6% yield) as a white crystalline solid. Mp 112-113° C. 1H NMR (300 MHz, CDCl3) δ 7.67 (m, 3H), 7.37 (m, 1H), 7.14 (m,2H), 5.26 (m, 2H), 4.78 (t, J=5.2 Hz, 1H), 4.21 (d, J=4.9 Hz, 1H), 4.02-3.77 (m, 5H), 3.92 (s, 3H), 1.56 (d, 3H, J=7.1 Hz); LRMS (APIMS) m/z 404 (MH+).

Workup

  1. customat room temperature
  2. washwashed H2O, brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customthe organic extracts were evaporated
  6. customThe product was purified by column chromatography on silica gel eluting with EtOAc:hexane (3:7 to 1:1)

Sources & evidence

ORD record
ord-a775ed4635ce4871b48384ea351b2336
Source dataset
uspto-grants-2012_07
Patent number
US08222277B2

Reaction notes

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