Dicyclohexylcarbodiimide → HCID 86600943, compound

HRID 1374066Notes

Reaction equation

HRID 1374066 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.O[CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[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][CH2:19][CH2:20][NH:21][C:22]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:28])=[O:15])[CH:7]=[CH:6]2

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 156391NaproxenHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamate

Product 1

HCID 86600943HCID 86600943, compoundYield 82.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 7.60 g, 33.0 mmol), tert-butyl N-(2-hydroxyethyl)carbamate (5.30 g, 32.9 mmol), N,N-dimethylaminopyridine (DMAP, 0.35 g, 2.86 mmol) and 1,3-dicyclohexylcarbodiimide (6.80 g, 33.0 mmol) in CH2Cl2 (200 mL) was stirred at ambient temperature overnight. The byproduct, dicyclohexyl urea, was removed by filtration. The filtrate was concentrated, dissolved in EtOAc (50 mL) and then cooled in a dry-ice bath to precipitate the remaining dicyclohexyl urea and then filtered. The filtrate was concentrated, dissolved in CH2Cl2 (15 mL) and hexane (200 mL) and then stirred until the product precipitated. The solid was dried under vacuum to give the title compound (10.12 g, 82% yield). Mp 82–84° C. 1H NMR (300 MHz, CDCl3) δ 7.72–7.65 (m, 3H), 7.42–7.38 (m, 1H), 7.16–7.11 (m, 2H), 5.05 (br, 1H), 4.13 (t, J=5.3 Hz, 2H), 3.91 (s, 3H), 3.87 (q, J=7.1 Hz, 1H), 3.30 (br. q, 2H), 1.58 (d, J=7.1 Hz, 3H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3) δ 174.4, 157.6, 155.6, 135.4, 133.6, 129.2, 128.8, 127.1, 126.0, 125.8, 119.0, 105.5, 79.3, 63.7, 55.2, 45.2, 39.5, 28.2, 18.3. Mass spectrum (API-TIS) m/z 374 (MH)+. Anal. calcd. for C21H27NO5: C, 67.54; H, 7.29; N, 3.75. Found: C, 67.43; H, 7.16; N, 3.66.

Workup

  1. customThe byproduct, dicyclohexyl urea, was removed by filtration
  2. concentrationThe filtrate was concentrated
  3. dissolutiondissolved in EtOAc (50 mL)
  4. temperaturecooled in a dry-ice bath
  5. customto precipitate the remaining dicyclohexyl urea
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. dissolutiondissolved in CH2Cl2 (15 mL)
  9. customprecipitated
  10. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-1e6bc73bb22446e2ae56ba67dda899fe
Source dataset
uspto-grants-2007_01
Patent number
US07163958B2

Reaction notes

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