Reaktion #2141310

Reaktionsgleichung

6-nitrophthalide

AlCl3

triethylamine

EtOAc

→

compound ( 20 )

Ausbeute 30.6%

ortho-Hydroxymethyl benzamide

Ausbeute 30.6%

Lösungsmittel

1,2-dichloroethane

1,2-dichloroethane

1,2-dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm up at room temperature
2. 2
   workup.STIRRINGthe mixture was stirred at room temperature overnight
3. 3
   SonstigeThe reaction mixture was then quenched with an ice-water mixture (30 ml)
4. 4
   workup.STIRRINGstirred for an additional 30 min
5. 5
   FiltrationThe resulting suspension was filtered through a bed of Celite®
6. 6
   Waschenthe filter cake was washed with 1,2-dichloroethane (10 ml)
7. 7
   SonstigeThe organic phase of the combined filtrates was separated
8. 8
   Waschenwashed with water (30 ml) and brine (20 ml)
9. 9
   Trocknendried over MgSO4
10. 10
    Einengenconcentrated
11. 11
    SonstigeThe crude product was purified by flash chromatography (35-75% EtOAc in hexanes, gradient elution)

Vorschrift

A solution of triethylamine (TEA, 0.658 g, 0.91 ml, 6.50 mmol, 1.5 equiv.) in 1,2-dichloroethane (3 ml) was added dropwise under stirring and cooling with ice to a suspension of AlCl3 (0.635 g, 4.76 mmol, 1.1 equiv.) in 1,2-dichloroethane (7 ml). The temperature was maintained at 15-20° C. during the addition and the mixture was then allowed to warm up at room temperature. A solution of 1-dimethoxytrityl-6-amino-hexan-1-ol (16) (2.00 g, 4.76 mmol, 1.1 equiv., prepared as described by Woo and Fung (1996), International Pat. App. Pub. No. WO 96/05215) and 6-nitrophthalide (18) (0.766 g, 4.33 mmol, 1.0 equiv.) in 1,2-dichloroethane (3 ml) was added over a period of 20 min and the mixture was stirred at room temperature overnight. The completion of the reaction was confirmed by TLC analysis (EtOAc containing 1% TEA). The reaction mixture was then quenched with an ice-water mixture (30 ml) and stirred for an additional 30 min. The resulting suspension was filtered through a bed of Celite® and the filter cake was washed with 1,2-dichloroethane (10 ml). The organic phase of the combined filtrates was separated, washed with water (30 ml) and brine (20 ml), dried over MgSO4 and concentrated. The crude product was purified by flash chromatography (35-75% EtOAc in hexanes, gradient elution) yielding 0.20 g (8%) of compound (20) as a pale yellow oil. Rf=0.2 (hexanes/EtOAc 1:1, v/v, containing 1% TEA). 1H NMR (300 MHz, CD3CN) δ 8.32-8.27 (m, 2H), 7.76-7.73 (m, 1H), 7.47-7.44 (m, 2H), 7.33-7.20 (m, 8H), 6.87 (d, J=9.1 Hz, 4H), 4.69 (d, J=5.9 Hz, 2H), 4.14 (t, J=5.9 Hz, 1H), 3.77 (s, 6H), 3.35 (q, J=6.5 Hz, 2H), 3.03 (t, J=6.4 Hz, 2H), 1.64-1.55 (m, 4H), 1.43-1.28 (m, 4H). 13C NMR (75 MHz, CD3CN) δ 167.4, 158.8, 147.7, 145.9, 136.9, 130.1, 128.2, 128.0, 126.9, 125.1, 122.9, 113.2, 85.8, 63.3, 62.3, 55.1, 39.8, 29.8, 29.1, 26.7, 26.0.

Quelle