반응 #1702084

반응 방정식

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

수율 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

수율 6.6%

용매

THF

반응 조건

후처리

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued at −78° C. for a further 5 min
3. 3
   온도to warm to room temperature
4. 4
   온도The reaction mixture was cooled to 0° C.
5. 5
   기타quenched with saturated aqueous NH4Cl
6. 6
   기타partitioned between water and ethyl acetate
7. 7
   추출The aqueous phase was extracted with ethyl acetate
8. 8
   세척The combined organic layers were washed with brine
9. 9
   건조dried over magnesium sulfate
10. 10
    여과filtered
11. 11
    농축concentrated
12. 12
    기타The residue was purified by silica gel column chromatography
13. 13
    기타further purified by HPLC (Gemini column
14. 14
    기타water, 5 min
15. 15
    기타water, 18 min
16. 16
    기타100% acetonitrile, 6 min
17. 17
    workup.ADDITIONboth solvents containing 0.1% trifluoroacetic acid),

실험 절차

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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