Reaktion #1803441

Reaktionsgleichung

2-chloro-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone

2-(Benzo[b]thiophen-2-ylthio)-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone

Crude compound 72

Benzo[b]thiophene-2-thiol

HCl

sulfur

nBuLi

NaH

→

compound 5

1,2,3,4-tetrahydro-benzo[b]azepin-5-one

Lösungsmittel

THF

THF

Et2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Temperaturto slowly warm up to RT over 3 h
3. 3
   ExtraktionThe thiol was extracted with ether
4. 4
   Waschenwashed with brine
5. 5
   Trocknendried over Na2SO4
6. 6
   Einengenconcentrated
7. 7
   Sonstigeto afford 2.0 g of crude compound 72 which
8. 8
   Sonstigewas used in the next step without further purification
9. 9
   workup.STIRRINGstirred for 30 min at RT
10. 10
    Temperaturcooled down to 0° C
11. 11
    workup.STIRRINGThe formed suspension was stirred for 40 min at 0° C.
12. 12
    workup.STIRRINGThe reaction mixture was stirred at RT for 16 h

Vorschrift

Compound 71 (1.75 g, 13.0 mmol) was dissolved in 40 mL of dry Et2O under N2 and the solution was cooled to 40° C. nBuLi (2.5 M solution in hexane, 5.7 mL, 14.3 mmol) was added and the reaction mixture was allowed to warm up to 0° C. during 1 h and then sulfur (0.414 g, 13.0 mmol) was added in one portion. The solution was allowed to slowly warm up to RT over 3 h. Excess of 10% HCl was added and the reaction mixture was stirred for 20 min. The thiol was extracted with ether, washed with brine, dried over Na2SO4 and concentrated to afford 2.0 g of crude compound 72 which was used in the next step without further purification. 2-(Benzo[b]thiophen-2-ylthio)-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone (73): Crude compound 72 (0.71 g, 4.3 mmol) was dissolved in 40 mL of dry THF under N2, stirred for 30 min at RT and then cooled down to 0° C. NaH (60% in mineral oil, 0.224 g, 5.5 mmol) was added to the ice-cold solution which became a yellowish suspension. The formed suspension was stirred for 40 min at 0° C. and then 2-chloro-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone (0.89 g, 4.3 mmol) was added as a solution in 4 mL of dry THF. The reaction mixture was stirred at RT for 16 h. The work-up, the same as for compound 5, gave crude material which was purified by flash chromatography (CH2Cl2/EtOAc) giving 0.56 g of the crude product. Pumping the crude product under high vacuum over P4O10 at 45° C. for 4 h removed the co-crystallized EtOAc to yield the desired product 73 (36%): MS: m/z+ 340.1 [M+H]+; Anal. Calcd (found) for C19H17NOS2: C, 67.22; (67.18), H, 5.05; (5.11), N, 4.13; (4.08), S, 18.89; (18.70).

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