반응 #1702106

반응 방정식

(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

수율 56.0%

용매

dichloroethane

—

hexanes

—

hexanes

반응 조건

후처리

1. 1
   기타sealed with
2. 2
   기타a cap
3. 3
   온도the temperature was increased to 90° C.
4. 4
   온도The reaction mixture was further heated to 100° C.
5. 5
   workup.STIRRINGstirred 24 h
6. 6
   기타partitioned between water and ethyl acetate:hexanes (1:1)
7. 7
   기타The layers were separated
8. 8
   추출the aqueous layer was extracted again with ethyl acetate:hexanes (1:1)
9. 9
   건조The combined organic layers were dried over sodium sulfate
10. 10
    여과filtered
11. 11
    농축concentrated

실험 절차

(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.

출처