Triethylamine → HCID 21075935, compound

HRID 1374063Notes

Reaction equation

HRID 1374063 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.[OH:18][CH2:19][CH2:20][O:21][C:22]1[CH:31]=[CH:30][C:25]([O:26][CH2:27][CH2:28]O)=[CH:24][CH:23]=1.Cl.CN(C)CCCN=C=NCC.CCN(CC)CC>CN(C=O)C>[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][CH2:28][CH2:27][O:26][C:25]1[CH:30]=[CH:31][C:22]([O:21][CH2:20][CH2:19][OH:18])=[CH:23][CH:24]=1)=[O:15])[CH:7]=[CH:6]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 669122,2'-[1,4-Phenylenebis(oxy)]diethanolHCID 156391NaproxenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 21075935HCID 21075935, compoundYield 79.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 4.27 g, 18.5 mmol), hydroquinone bis(2-hydroxyethyl) ether (10.6 g, 53.3 mmol), N,N-dimethylaminopyridine (DMAP, 2.71 g, 22.2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (9.34 g, 48.7 mmol) and NEt3 (13 mL, 93.3 mmol) in DMF (100 mL) was stirred at ambient temperature overnight. The reaction mixture was evaporated to dryness under vacuum and the residue was partitioned between HCl (3N, 100 mL) and CH2Cl2 (200 mL). The organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated. The product was separated by silica gel column chromatography eluting with EtOAc/hexane (1:1, Rf=0.15) and then recrystalized from ethyl ether and hexane to give the title compound as a white solid (6.01 g, 31% yield). Mp 76–78° C. 1H NMR (CDCl3) δ 7.7–7.64 (m, 3H), 7.42–7.38 (m, 1H), 7.15–7.08 (m, 2H), 6.74–6.72 (m 4H), 4.45–4.36 (m, 2H), 4.1–3.85 (m, 7H), 3.90 (s, 3H), 2.13 (br. t, 1H), 1.58 (d, J=7.2 Hz, 3H). 13C NMR (CDCl3) δ 174.6, 157.5, 153.0, 152.8, 135.4, 133.6, 129.2, 128.8, 127.1, 126.1, 125.9, 118.8, 115.7, 115.3, 105.5, 69.7, 66.6, 63.1, 61.4, 55.2, 45.2, 18.4. MS(API) m/z 428 (M+NH4)+. Anal. calcd. for C24H26O6: C, 70.23; H, 6.38. Found: C, 70.01; H, 6.39.

Workup

  1. customThe reaction mixture was evaporated to dryness under vacuum
  2. customthe residue was partitioned between HCl (3N, 100 mL) and CH2Cl2 (200 mL)
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was separated by silica gel column chromatography
  8. washeluting with EtOAc/hexane (1:1, Rf=0.15)
  9. customrecrystalized from ethyl ether and hexane

Sources & evidence

ORD record
ord-ed416043094d47e9b4d7b19a9fe7c74c
Source dataset
uspto-grants-2007_01
Patent number
US07163958B2

Reaction notes

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