反应 #1702084

反应方程式

Methyl 5-(3,3-Dimethyl-but-1-ynyl)-3-[(1-methoxy-1-oxo-1λ5phosphinan-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylate

KHMDS

Trans-4-methylcyclohexanecarbonyl chloride

→

title compound

收率 6.6%

methyl 5-(3,3-Dimethyl-but-1-ynyl)-3-[(1-methoxy-1-oxo-1 λ5-phosphinan-4-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylate

收率 6.6%

溶剂

THF

反应条件

后处理

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued at −78° C. for a further 5 min
3. 3
   温度to warm to room temperature
4. 4
   温度The reaction mixture was cooled to 0° C.
5. 5
   其他quenched with saturated aqueous NH4Cl
6. 6
   其他partitioned between water and ethyl acetate
7. 7
   萃取The aqueous phase was extracted with ethyl acetate
8. 8
   洗涤The combined organic layers were washed with brine
9. 9
   干燥dried over magnesium sulfate
10. 10
    过滤filtered
11. 11
    浓缩concentrated
12. 12
    其他The residue was purified by silica gel column chromatography
13. 13
    其他further purified by HPLC (Gemini column
14. 14
    其他water, 5 min
15. 15
    其他water, 18 min
16. 16
    其他100% acetonitrile, 6 min
17. 17
    workup.ADDITIONboth solvents containing 0.1% trifluoroacetic acid),

实验过程

Methyl 5-(3,3-Dimethyl-but-1-ynyl)-3-[(1-methoxy-1-oxo-1λ5phosphinan-4-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylate (420 mg, 1.1 mmol) was dissolved in 2 mL of THF and cooled to −78° C. with a dry ice-acetone bath. A solution of KHMDS (2.6 mL, 0.5 M in toluene) was added slowly, and the mixture was stirred for 5 min. Trans-4-methylcyclohexanecarbonyl chloride (210 mg, 1.3 mmol) was added dropwise and stirring was continued at −78° C. for a further 5 min. The mixture was then allowed to warm to room temperature. The reaction mixture was cooled to 0° C. and quenched with saturated aqueous NH4Cl, and then partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography using 10% MeOH in EtOAc Hexanes as eluent and then further purified by HPLC (Gemini column; 5% acetonitrile:water, 5 min; 5-100% acetonitrile:water, 18 min; 100% acetonitrile, 6 min; both solvents containing 0.1% trifluoroacetic acid), resulting in the title compound (37 mg) and recovered starting material (210 mg). MS (m/z): 508.2 [M+H]+; HPLC retention time: 4.949 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

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