反应 #1702106

反应方程式

(1S)-4-Methyl-cyclohex-3-ene-1-carboxylic acid chloride

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

EtOAc

EtOAc

→

5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

收率 56.0%

溶剂

dichloroethane

—

hexanes

—

hexanes

反应条件

后处理

1. 1
   其他sealed with
2. 2
   其他a cap
3. 3
   温度the temperature was increased to 90° C.
4. 4
   温度The reaction mixture was further heated to 100° C.
5. 5
   workup.STIRRINGstirred 24 h
6. 6
   其他partitioned between water and ethyl acetate:hexanes (1:1)
7. 7
   其他The layers were separated
8. 8
   萃取the aqueous layer was extracted again with ethyl acetate:hexanes (1:1)
9. 9
   干燥The combined organic layers were dried over sodium sulfate
10. 10
    过滤filtered
11. 11
    浓缩concentrated

实验过程

(1S)-4-Methyl-cyclohex-3-ene-1-carboxylic acid chloride (1.8 mmol), 5-(3,3-dimethyl-but-1-ynyl)-3-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-thiophene-2-carboxylic acid methyl ester (336 mg, 0.89 mmol) and DMAP (217 mg, 1.8 mmol) were dissolved in dichloroethane (2.2 mL), sealed with a cap and heated to 80° C. After 2 h, the temperature was increased to 90° C., and the solution was stirred 16 h. The reaction mixture was further heated to 100° C., stirred 24 h and partitioned between water and ethyl acetate:hexanes (1:1). The layers were separated and the aqueous layer was extracted again with ethyl acetate:hexanes (1:1). The combined organic layers were dried over sodium sulfate, filtered and concentrated. Flash chromatography (5% EtOAc:hexanes 5 min then 5-40% EtOAc:hexanes, 20 min, 24 g column) afforded 250 mg (56% yield of the desired 5-(3,3-dimethyl-but-1-ynyl)-3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(4-methyl-cyclohex-3-enecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester as a white foam.

来源