Reaktion #1859515

Reaktionsgleichung

potassium tert-butoxide

(2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone

acetic acid

(1S,2R)-ethyl 1-((diphenylmethylene)amino)-2-(methoxymethyl)cyclopropanecarboxylate

→

(1S,2R)-5′-(4-chlorophenyl)-2-(methoxymethyl)-6′,7′-dimethylspiro[cyclopropane-1,3′-thieno[2,3-e][1,4]diazepin]-2′(1′H)-one

Lösungsmittel

THF

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstige(over 5 min)
2. 2
   workup.ADDITIONwere added at 60° C
3. 3
   workup.DISTILLATIONTHF was distilled off
4. 4
   Temperaturthe reaction was heated
5. 5
   Temperaturto reflux for 3 h
6. 6
   workup.ADDITIONwas added
7. 7
   Sonstigethe solvent was removed under vacuum
8. 8
   Sonstigethe product was purified by flash chromatography (EtOAc/hexane 1:19 to 6:14)

Vorschrift

To a solution of (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (7.09 g, 26.7 mmol) and (1S,2R)-ethyl 1-((diphenylmethylene)amino)-2-(methoxymethyl)cyclopropanecarboxylate (6 g, 17.78 mmol) in anhydrous THF (100 mL) was slowly (over 5 min) added a solution of potassium tert-butoxide (1 M in THF) at rt. The reaction was heated to 60° C. for approximately 20 h before acetic acid (10.68 g, 178 mmol) and absolute ethanol (20 mL) were added at 60° C. THF was distilled off, and the reaction was heated to reflux for 3 h. The reaction was cooled to rt before silica gel was added, and the solvent was removed under vacuum. The dry silica gel was packed and the product was purified by flash chromatography (EtOAc/hexane 1:19 to 6:14) to give (1S,2R)-5′-(4-chlorophenyl)-2-(methoxymethyl)-6′,7′-dimethylspiro[cyclopropane-1,3′-thieno[2,3-e][1,4]diazepin]-2′(1′H)-one a solid (3.7 g). LRMS (M+H)+: 375 m/z.

Quelle