Methyl iodide → Methyl 5-{4-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-4-pentynoate

4-Pentynoic acid (0.50 g, 5.0 mmol) was dissolved in DMF (15 mL). To this solution was added K2CO3 (2.76 g, 20 mmol) followed by CH3I (0.95 mL, 15 mmol). The reaction mixture was stirred at room temperature overnight. Water was added to dissolve all solid, and the mixture was extracted with ether (2×75 mL). The organic extracts were combined and washed with saturated NaHCO3, water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude methyl 4-pentynoate as colorless oil (0.29 g, 52%). To a degassed solution of 4-[(4-Iodophenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenol (144) (0.25 g, 0.56 mmol) in DMF (5 mL) were added Pd(PPh3)2Cl2 (40 mg, 0.06 mmol), CuI (11 mg, 0.06 mmol), N,N-diisopropylethylamine (0.45 mL, 2.52 mmol) and methyl 4-pentynoate (0.15 g). The reaction mixture was stirred at room temperature overnight, poured into saturated aqueous NH4Cl (15 mL) and water (5 mL), extracted with ethyl acetate (2×50 mL). The combined organic phase washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as brown oil. The crude product was purified by chromatography on a silica gel column eluted with a gradient from hexanes to 20% EtOAc in hexanes to give a light brown solid. The solid was triturated with hot hexanes containing 1% to afford 184 mg (76%) of the title compound (243) as off-white solid. mp 159-160° C. 1H NMR (400 MHz, CDCl3): δ 0.90 (s, 6H), 0.91 (s, 6H), 1.27 (s, 2H), 1.92 (s, 2H), 1.96 (s, 2H), 2.55-2.65 (m, 2H), 2.65-2.75 (m, 2H), 3.71 (s, 3H), 4.58 (s, 1H), 6.72 (d, J=8.4 Hz, 2H), 7.00 (d, J=8.4 Hz, 2H), 7.06 (d, J=8.2 Hz, 2H), 7.28 (d, J=8.3 Hz, 2H). LCMS (ESI): m/z 431 (M+H)+, 429 (M−H)−.

1. dissolutionto dissolve all solid
2. extractionthe mixture was extracted with ether (2×75 mL)
3. washwashed with saturated NaHCO3, water, brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate was concentrated
7. customto give the crude methyl 4-pentynoate as colorless oil (0.29 g, 52%)
8. stirringThe reaction mixture was stirred at room temperature overnight
9. extractionextracted with ethyl acetate (2×50 mL)
10. washThe combined organic phase washed with water, brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationthe filtrate was concentrated
14. customto give the crude product as brown oil
15. customThe crude product was purified by chromatography on a silica gel column
16. washeluted with a gradient from hexanes to 20% EtOAc in hexanes
17. customto give a light brown solid
18. customThe solid was triturated with hot hexanes containing 1%

ORD record

ord-7c7efce453cc4506bba339f590cbdb7b

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07569601B2