Reaktion #61358

Reaktionsgleichung

water

Sodium hydride

Boc-4(R)-hydroxyproline

1-(bromomethyl) naphthalene

→

title compound

Ausbeute 56.2%

Boc-4(R)-(naphthalen-1-ylmethoxy)proline

Ausbeute 56.2%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITION, (1981), 59, 2629-2641) was added
2. 2
   Temperaturthe mixture was heated
3. 3
   Temperaturat reflux for 18 h
4. 4
   Waschenwashed with hexane
5. 5
   Extraktionextracted twice with ethyl acetate
6. 6
   Waschenwashed with brine
7. 7
   Trocknendried (MgSO4)
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated
10. 10
    SonstigeThe residue was purified by flash chromatography (49:49:2 hexane:ethyl acetate:acetic acid)

Vorschrift

Commercially available Boc-4(R)-hydroxyproline (5.00 g, 21.6 mmol) was dissolved in THF (100 mL) and cooled to 0° C. Sodium hydride (60% dispersion in oil, 1.85 g, 45.4 mmol) was added portionwise over 10 minutes and the suspension was stirred at RT for 1 h. Then, 1-(bromomethyl) naphthalene (8.00 g, 36.2 mmol) (prepared as described in E. A. Dixon et al. Can. J. Chem., (1981), 59, 2629-2641) was added and the mixture was heated at reflux for 18 h. The mixture was poured into water (300 mL) and washed with hexane. The aqueous layer was acidified with 10% aqueous HCl and extracted twice with ethyl acetate. The organic layers were combined and washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (49:49:2 hexane:ethyl acetate:acetic acid) to give the title compound as a colorless oil (4.51 g, 56% yield). 1H NMR (DMSO-d6) indicated the presence of two rotamers: δ 8.05 (m, 1H), 7.94 (m, 1H), 7.29 (d, J=14 Hz, 1H), 7.55-7.45 (m, 4H), 4.96 (m, 2H), 4.26 (br. s, 1H), 4.12 (dd, J=8 Hz, 1H), 3.54-3.42 (m, 2H), 2.45-2.34 (m, 1H), 2.07-1.98 (m, 1H), 1.36 (s, (3/9) 9H), 1.34 (s, (6/9) 9H).

Quelle