Reaktion #332072

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

Trans-4-methylcyclohexyl Carboxylic Acid Chloride

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

Vorschrift

The 1M solution of trans-4-methylcyclohexyl carboxylic acid chloride is 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 is then stirred for 16 h at reflux. The reaction mixture is 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 is stirred 2 h at 5° C. The white suspension is filtered off and the toluene is added to the mother liquor. The organic phase is washed with 10% citric acid, aq. Sat NaHCO3, dried (Na2SO4) and concentrated. The residue is triturated in boiling hexane (1500 mL). The reaction mixture is allowed to cool down to room temperature. The reaction flask is immersed into ice bath, and stirred for 30 min; white solid is filtered off, and washed with cold hexane (225 mL). The solid is purified by silica gel column chromatography using 20% EtOAc:hexane as eluent to furnish 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%).

Quelle