反応 #1702100

反応方程式

[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

収率 92.3%

溶媒

1,2-dichloroethane

CH2Cl2

DMF

CH2Cl2

反応条件

後処理

1. 1
   濃縮concentrated
2. 2
   濃縮concentrated
3. 3
   温度The solution was warmed to room temperature
4. 4
   workup.STIRRINGstirred overnight
5. 5
   洗浄twice washed with saturated NH4Cl(aq)
6. 6
   乾燥dried over MgSO4
7. 7
   ろ過filtered
8. 8
   濃縮concentrated
9. 9
   その他purified by silica gel column chromatography
10. 10
    洗浄eluting with a mixture of 0-75% EtOAc/hexanes

実験手順

(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.

出典