反応 #61358

反応方程式

water

Sodium hydride

Boc-4(R)-hydroxyproline

1-(bromomethyl) naphthalene

→

title compound

収率 56.2%

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

収率 56.2%

溶媒

THF

反応条件

後処理

1. 1
   workup.ADDITION, (1981), 59, 2629-2641) was added
2. 2
   温度the mixture was heated
3. 3
   温度at reflux for 18 h
4. 4
   洗浄washed with hexane
5. 5
   抽出extracted twice with ethyl acetate
6. 6
   洗浄washed with brine
7. 7
   乾燥dried (MgSO4)
8. 8
   ろ過filtered
9. 9
   濃縮concentrated
10. 10
    その他The residue was purified by flash chromatography (49:49:2 hexane:ethyl acetate:acetic acid)

実験手順

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).

出典