反応 #1869172

反応方程式

2-methoxy-17-oxoestra-1,3,5(10)-triene-3-yl(trifluoromethyl)sulfonate

2-Methoxy-17-oxoestra-1,3,5(10)-trien-3-yl (trifluoromethyl)sulfonate

Compound 42

2-Methoxy-17-oxoestra-1,3,5(10)-trien-3-yl (trifluoromethyl)sulfonate

1,3-bis(diphenylphosphino)propane

1,1,1,3,3,3-hexamethyldisilazane

dimethylformamide

→

Compound 54

収率 44.0%

2-methoxy-17-oxoestra-1,3,5(10)-triene-3-carboxamide

収率 44.0%

反応条件

後処理

1. 1
   温度reflux condenser, nitrogen inlet
2. 2
   その他Carbon monoxide was bubbled through the yellow solution
3. 3
   workup.STIRRINGto stir for 15 h
4. 4
   workup.WAITDuring this period the reaction became dark
5. 5
   その他The reaction was quenched
6. 6
   workup.ADDITIONby treating with methanol (25 mL)
7. 7
   workup.STIRRINGstirred for 10 min
8. 8
   workup.ADDITIONThe mixture was poured into ethyl acetate (1 L)
9. 9
   洗浄washed with 2N sulfuric acid (750 mL)
10. 10
    抽出The aqueous layer was extracted with ethyl acetate (2×500 mL)
11. 11
    洗浄the combined organic phases were washed with 2N sulfuric acid (250 mL) and saturated aqueous sodium bicarbonate (500 mL)
12. 12
    乾燥then dried over 500 g of sodium sulfate
13. 13
    ろ過This mixture was suction-filtered through a bed of silica gel 60 (67 g)
14. 14
    濃縮concentrated to dryness
15. 15
    その他affording crude product (11.2 g, 98% recovery)
16. 16
    その他The crude material was purified by Flash column chromatography (360 g of silica gel 60
17. 17
    洗浄eluting with methylene chloride
18. 18
    乾燥Concentration of the pure fractions (Rf=0.3, 1:5 ethyl acetete:methylene chloride, UV detection) and drying in a vacuum oven at 50° C.
19. 19
    その他removal of residual solvents

実験手順

A 1-L 3 neck round-bottomed flask equipped with an overhead stirrer, reflux condenser, nitrogen inlet and thermocouple, was charged with 2-methoxy-17-oxoestra-1,3,5(10)-triene-3-yl(trifluoromethyl)sulfonate (Scheme 5, Compound 42) (15 g, 34.7 mmol), 1,3-bis(diphenylphosphino)propane (1.54 g, 3.73 mmol), palladium (II) chloride (0.33 g, 1.9 mmol), 1,1,1,3,3,3-hexamethyldisilazane (31 mL, 150 mmol) and anhydrous dimethylformamide (110 mL). Carbon monoxide was bubbled through the yellow solution while stirring for 5 minutes. The reaction was heated to 110° C. under an atmosphere of carbon monoxide (balloon) and allowed to stir for 15 h. During this period the reaction became dark. The reaction was quenched by treating with methanol (25 mL) and stirred for 10 min. The mixture was poured into ethyl acetate (1 L) and washed with 2N sulfuric acid (750 mL). The aqueous layer was extracted with ethyl acetate (2×500 mL) and the combined organic phases were washed with 2N sulfuric acid (250 mL) and saturated aqueous sodium bicarbonate (500 mL) then dried over 500 g of sodium sulfate. This mixture was suction-filtered through a bed of silica gel 60 (67 g) and concentrated to dryness affording crude product (11.2 g, 98% recovery). The crude material was purified by Flash column chromatography (360 g of silica gel 60, eluting with methylene chloride, then 1:5 ethyl acetate:methylene chloride). Concentration of the pure fractions (Rf=0.3, 1:5 ethyl acetete:methylene chloride, UV detection) and drying in a vacuum oven at 50° C., and removal of residual solvents afforded pure product (Scheme 5, Compound 54) (4.97 g, 44% yield) as an off-white to pale yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.99 (s, 1H), 7.82 (br s, 1H), 7.05 (s, 1H), 5.92 (br s, 1H), 4.02 (s, 3H), 3.05 (dd, 2H, J=5), 2.15 (m 2H,) 2.02-1.65 (m, 6H), 1.55-1.15 (m, 8H), 0.80 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 220.6, 167.2, 155.9, 145.5, 132.8, 129.4, 118.3, 108.4, 55.9, 50.5, 47.9, 44.9, 37.8, 35.8, 31.6, 28.26, 26.4, 25.8, 21.6, 13.8.

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