Reaktion #1132540

Reaktionsgleichung

3-(Trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine dichloride

triethyl amine

1-(tert-butoxycarbonyl)-3-(methoxymethyl)pyrrolidine-3-carboxylic acid

oxalyl chloride dichloromethane

→

title compound

tert-Butyl 3-(methoxymethyl)-3-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)pyrrolidine-1-carboxylate

Lösungsmittel

dichloromethane

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated to dryness under the reduced pressure
2. 2
   workup.STIRRINGThe mixture was stirred at 0° C. for 1 h
3. 3
   Waschenwashed with sodium bicarbonate solution (2×50 mL) and water (3×100 mL)
4. 4
   Trocknendried over sodium sulfate
5. 5
   Sonstigepurified by silica chromatography

Vorschrift

The title compound was prepared according to general procedure C described in connection with Scheme 2. To 1-(tert-butoxycarbonyl)-3-(methoxymethyl)pyrrolidine-3-carboxylic acid (3 g, 11.6 mmol) in dichloromethane (30 mL) was added 2M oxalyl chloride dichloromethane solution (17 mL, 34 mmole) and a few drops of DMF at room temperature. The mixture was stirred at RT for 2 hours and concentrated to dryness under the reduced pressure. 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine dichloride (3.19 g, 11.6 mmole) in 30 dichloromethane and triethyl amine (3.1 g, 30 mmole) was added to the above residue at 0° C. The mixture was stirred at 0° C. for 1 h, diluted with dichloromethane (100 mL) and washed with sodium bicarbonate solution (2×50 mL) and water (3×100 mL), dried over sodium sulfate and purified by silica chromatography using 2.5% MeOH in CH2Cl2 as eluent to give product (1.7 g, 33% yield). 1H NMR (400 MHz, CD3OD): δ 8.70 (s, 1H), 7.68 (m, 1H), 4.80 (s, 2H), 4.10-2.95 (m, 13H), 2.40-2.15 (m, 2H), 1.48 (s, 9H); MS (ESI) m/z: Calculated for C21H28F3N3O4: 443.2. found: 466 (M+Na)+.

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