Reaction #1755467

Reaction equation

compound 84

Toluene-4-sulfonic acid 4-(tert-butyl-dimethyl-silanyloxymethyl)-cyclohexylmethyl ester

ammonia

ammonia

lithium

Acetylene

acetylene

lithium

→

86

Yield 93.0%

(4-Prop-2-ynyl-cyclohexyl)-methanol

Yield 93.0%

Solvents

THF

DMSO

Conditions

Workup

1. 1
   OtherA 3-neck 250 mL-flask equipped with a gas inlet tube and dry-ice condenser
2. 2
   Otherhad reacted
3. 3
   Otherthe acetylene-inlet tube and condenser removed
4. 4
   workup.ADDITIONDMSO (20 mL) was added
5. 5
   Otherthe ammonia evaporated with a warm water bath until the mixture
6. 6
   Othera temperature of 30° C
7. 7
   workup.STIRRINGThe solution was stirred at this temperature for 2 hours until the solution
8. 8
   Otherstopped bubbling
9. 9
   TemperatureThe mixture was cooled to 5° C.
10. 10
    TemperatureThe temperature was maintained at 5° C
11. 11
    workup.STIRRINGto stir at 5° C. for 0.5 hours
12. 12
    TemperatureThen the solution was gradually warmed to room temperature
13. 13
    workup.STIRRINGstirred for an additional 18 hours
14. 14
    Extractionextracted with ether (4×100 mL)
15. 15
    Dryingdried with anhydrous sodium sulfate
16. 16
    Concentrationconcentrated in vacuo
17. 17
    Otherto yield a yellow oil
18. 18
    workup.STIRRINGto stir for 24 hours 2 under N2 atmosphere
19. 19
    workup.STIRRINGAfter stirring
20. 20
    Otherthe reaction was quenched with water (200 mL)
21. 21
    Extractionextracted with ether (3×100 mL)
22. 22
    Concentrationconcentrated in vacuo
23. 23
    OtherThe crude product was purified by chromatography, on a silica gel column
24. 24
    Washeluting with 1:1 ether/petroleum ether

Procedure

A 3-neck 250 mL-flask equipped with a gas inlet tube and dry-ice condenser was cooled to −78° C. and charged with liquid ammonia (40 mL). To the reaction mixture was added lithium wire (600 mg, 86.4 mmol) generating a deep blue solution. The mixture was allowed to stir for 1 hour. Acetylene, passed through a charcoal drying tube, was added to the ammonia until all the lithium had reacted and the solution turned colorless, at which time the flow of acetylene was stopped, the acetylene-inlet tube and condenser removed and the flask outfitted with a thermometer. DMSO (20 mL) was added and the ammonia evaporated with a warm water bath until the mixture reached a temperature of 30° C. The solution was stirred at this temperature for 2 hours until the solution stopped bubbling. The mixture was cooled to 5° C. and compound 84 (11.25 g, 27.3 mmol), in DMSO (10 mL), was added. The temperature was maintained at 5° C. The mixture was allowed to stir at 5° C. for 0.5 hours. Then the solution was gradually warmed to room temperature and stirred for an additional 18 hours. The brown/black reaction mixture was poured slowly over ice (300 g) and extracted with ether (4×100 mL), dried with anhydrous sodium sulfate, and concentrated in vacuo to yield a yellow oil. The oil was subsequently dissolved in THF (200 mL) and changed to a brownish color upon addition of TBAF hydrate (11.20 g, 35.5 mmol). The solution was allowed to stir for 24 hours 2 under N2 atmosphere. After stirring, the reaction was quenched with water (200 mL) and extracted with ether (3×100 mL). The ether extracts were combined and concentrated in vacuo. The crude product was purified by chromatography, on a silica gel column, eluting with 1:1 ether/petroleum ether to yield 86 (3.91 g, 93%) as a yellow oil. 1H NMR (CDCl3) δ 3.45 (d, J=6.2, 2H), 2.10 (d, J=6.2, 2H), 1.9 (s, 1H), 1.94-1.69 (m, 4H), 1.52-1.34 (m, 2H), 1.16-0.83 (m, 4H); 13C NMR (CDCl3) δ 83.8, 69.5, 69.0, 40.8, 37.7, 32.3, 29.7, 26.5.

Source