반응 #1702100

반응 방정식

[5-(3,3-Dimethyl-but-1-ynyl)-thiophen-3-yl]-(1,4-dioxa-spiro[4.5]dec-8-yl)-amine

diisopropylethylamine

(COCl)2

(1S,6S)-4,6-dimethyl-cyclohex-3-ene-carboxylic acid

→

(1S,6S)-4,6-dimethyl-cyclohex-3-ene-carboxylic acid [5-(3,3-dimethyl-but-1-ynyl)-thiophen-3-yl]-(1,4-dioxa-spiro[4.5]dec-8-yl)-amide

수율 92.3%

용매

1,2-dichloroethane

CH2Cl2

DMF

CH2Cl2

반응 조건

후처리

1. 1
   농축concentrated
2. 2
   농축concentrated
3. 3
   온도The solution was warmed to room temperature
4. 4
   workup.STIRRINGstirred overnight
5. 5
   세척twice washed with saturated NH4Cl(aq)
6. 6
   건조dried over MgSO4
7. 7
   여과filtered
8. 8
   농축concentrated
9. 9
   기타purified by silica gel column chromatography
10. 10
    세척eluting with a mixture of 0-75% EtOAc/hexanes

실험 절차

(1S,6S)-4,6-dimethyl-cyclohex-3-ene-carboxylic acid (3.04 g, 19.7 mmol) was dissolved in CH2Cl2 (30 mL) and DMF (20 μL) was added. The solution was cooled to 0° C. and (COCl)2 (3.7 mL, 39 mmol) was added slowly. The reaction was stirred in an ice bath for 2 hours and then concentrated. The residue was taken up in hexanes and concentrated; this hexanes coevaporation was repeated once more. To the residue was added [5-(3,3-Dimethyl-but-1-ynyl)-thiophen-3-yl]-(1,4-dioxa-spiro[4.5]dec-8-yl)-amine (4.16 g, 13 mmol), diisopropylethylamine (4.5 mL, 26 mmol), and 1,2-dichloroethane (40 mL) at 0° C. The solution was warmed to room temperature and stirred overnight. The reaction was diluted with CH2Cl2, twice washed with saturated NH4Cl(aq), dried over MgSO4, filtered, concentrated, and purified by silica gel column chromatography, eluting with a mixture of 0-75% EtOAc/hexanes, to give (1S,6S)-4,6-dimethyl-cyclohex-3-ene-carboxylic acid [5-(3,3-dimethyl-but-1-ynyl)-thiophen-3-yl]-(1,4-dioxa-spiro[4.5]dec-8-yl)-amide (5.6 g, 12 mmol) as a single isomer.

출처