Reaktion #1781615

Reaktionsgleichung

pyridine

MeOH

trans-4-methylcyclohexyl carboxylic acid chloride

5-bromo-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester

pyridine

→

final compound

5-cyclohex-1-enyl-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid

5-Bromo-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

Ausbeute 32.0%

Lösungsmittel

toluene

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux
2. 2
   workup.STIRRINGthe mixture was stirred 2 h at 5° C
3. 3
   FiltrationThe white suspension was filtered off
4. 4
   workup.ADDITIONthe toluene was added to the mother liquor
5. 5
   WaschenThe organic phase was washed with 10% citric acid, aq. Sat NaHCO3
6. 6
   Trocknendried (Na2SO4)
7. 7
   Einengenconcentrated
8. 8
   SonstigeThe residue was triturated
9. 9
   Temperaturto cool down to room temperature
10. 10
    SonstigeThe reaction flask was immersed into ice bath
11. 11
    workup.STIRRINGstirred for 30 min
12. 12
    Filtrationwhite solid was filtered off
13. 13
    Waschenwashed with cold hexane (225 ml)
14. 14
    SonstigeThe solid was purified by silica gel column chromatography

Vorschrift

The 1M solution of trans-4-methylcyclohexyl carboxylic acid chloride was added to a solution of 5-bromo-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester (24.79 g, 65 mmol) in toluene (25 ml) followed by pyridine (5.78 ml, 71.5 mmol). The resulting mixture was then stirred for 16 h at reflux. The reaction mixture was diluted with toluene (60 ml) and cooled down to 5° C. After the addition of pyridine (12 ml) and MeOH (5.6 ml), the mixture was stirred 2 h at 5° C. The white suspension was filtered off and the toluene was added to the mother liquor. The organic phase was washed with 10% citric acid, aq. Sat NaHCO3, dried (Na2SO4) and concentrated. The residue was triturated in boiling hexane (1500 ml). The reaction mixture was allowed to cool down to room temperature. The reaction flask was immersed into ice bath, and stirred for 30 min; white solid was filtered off, and washed with cold hexane (225 ml). The solid was purified by silica gel column chromatography using 20% EtOAc:hexanes as eluent to furnished the final compound 5-Bromo-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (10.5 g, 32%). 1H NMR (CDCl3, 400 MHz): 6.84 (s, 1H), 4.62 (m, 1H), 3.90-3.82 (m, 4H), 3.80 (s, 3H), 1.92-1.81 (m, 2H), 1.77-1.11 (m, 14H), 1.79 (d, 3H), 0.77-0.59 (m, 2H).

Quelle