反応 #1702084

反応方程式

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

収率 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

収率 6.6%

溶媒

THF

反応条件

後処理

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
   その他quenched with saturated aqueous NH4Cl
6. 6
   その他partitioned between water and ethyl acetate
7. 7
   抽出The aqueous phase was extracted with ethyl acetate
8. 8
   洗浄The combined organic layers were washed with brine
9. 9
   乾燥dried over magnesium sulfate
10. 10
    ろ過filtered
11. 11
    濃縮concentrated
12. 12
    その他The residue was purified by silica gel column chromatography
13. 13
    その他further purified by HPLC (Gemini column
14. 14
    その他water, 5 min
15. 15
    その他water, 18 min
16. 16
    その他100% acetonitrile, 6 min
17. 17
    workup.ADDITIONboth solvents containing 0.1% trifluoroacetic acid),

実験手順

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).

出典