Reaction #1804

Reaction equation

product

3,9-Bis(trifluoromethanesulfonyloxy)-6-[4-[2-(1-piperidinyl)ethoxy]phenyl]-6-H-[1]benzothieno[3,2-c][1]benzopyran

diphenylphosphinopropane

formic acid

triethylamine

→

title compound

Yield 57.0%

6-[4-[2-(1-piperidinyl)ethoxy]phenyl]-6-H-[1]benzothieno[3,2-c][1]benzopyran

Yield 57.0%

Solvents

dimethylformamide

Conditions

Workup

1. 1
   ConcentrationAfter concentration
2. 2
   workup.ADDITIONProduct containing fractions
3. 3
   Concentrationwere concentrated
4. 4
   Otherpartitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL)
5. 5
   Extractionthe aqueous layer extracted with methylene chloride (50 mL)
6. 6
   DryingThe combined organic extracts were dried (sodium sulfate)
7. 7
   Concentrationconcentrated
8. 8
   Otherthe residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide)

Procedure

A solution of the product of Example 6 (780 mg, 1.06 mmol), palladium(II) acetate (42 mg, 0.19 mmol), 1,2-bis(diphenylphosphinopropane (149 mg, 0.36 mmol), formic acid (0.6 mL), and triethylamine (3.0 mL) in anhydrous dimethylformamide (40 mL) was stirred at ambient temperature for 4 d. After concentration, the residue was subjected chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide). Product containing fractions were concentrated, partitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL), and the aqueous layer extracted with methylene chloride (50 mL). The combined organic extracts were dried (sodium sulfate), concentrated, and the residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide) to give 267 mg (57%) of the title compound as an oil which gave a white, crystalline solid, mp 107° C., upon trituration with ether/hexane: 1H NMR (300 MHz, CDCl3) d 7.86 (d, J=7.4 Hz, 1H), 7.40 (m, 1H), 7.1-7.3 (m, 6H), 6.97 (t, J=7.3 Hz, 1H), 6.89 (d, J=8.1 Hz, 1H), 6.84 (d, J=8.6 Hz, 2H), 6.66 (s, 1H), 4.07 (t, J=6.1 Hz, 2H), 2.75 (t, J=6.1 Hz, 2H), 2.49 (m, 4H), 1.5-1.7 (m, 4H), 1.4-1.5 (m, 2H); 13C NMR (125 MHz, CDCl3) d 159.1, 151.6, 139.3, 137.1, 133.0, 131.5, 129.8, 129.1, 126.8, 124.6, 124.4, 123.7, 122.6, 121.5, 121.5, 119.3, 116.9, 114.6, 77.6, 65.7, 57.7, 54.9, 25.8, 24.0; MS (FD+) m/e 441 (M+); Anal. calc'd for C28H27NO2 S: C, 76.15; H, 6.17; N, 3.17. Found: C, 75.93; H, 6.44; N, 3.01.

Source