Реакция #1702084

Уравнение реакции

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

Выход 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

Выход 6.6%

Растворители

THF

Условия реакции

Обработка

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued at −78° C. for a further 5 min
3. 3
   Температураto warm to room temperature
4. 4
   ТемператураThe reaction mixture was cooled to 0° C.
5. 5
   Другоеquenched with saturated aqueous NH4Cl
6. 6
   Другоеpartitioned between water and ethyl acetate
7. 7
   ЭкстракцияThe aqueous phase was extracted with ethyl acetate
8. 8
   ПромывкаThe combined organic layers were washed with brine
9. 9
   Сушкаdried over magnesium sulfate
10. 10
    Фильтрацияfiltered
11. 11
    Концентрированиеconcentrated
12. 12
    ДругоеThe residue was purified by silica gel column chromatography
13. 13
    Другоеfurther purified by HPLC (Gemini column
14. 14
    Другоеwater, 5 min
15. 15
    Другоеwater, 18 min
16. 16
    Другое100% acetonitrile, 6 min
17. 17
    workup.ADDITIONboth solvents containing 0.1% trifluoroacetic acid),

Методика

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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