Org Prep Daily

October 5, 2006


Filed under: procedures — milkshake @ 12:49 am


The opticaly pure acetonide ester alcohol 1.981g (7.609mmol, obtained from Kaneka) was dissolved in anh dichloromethane 50mL, 2,6-lutidine 1.35mL (11.63 mmol) was added and the solution was cooled to -78C. Neat triflic anhydride 1.40mL (2.36g, 8.345 mmol) was added dropwise and the mixture was stirred at -78C for 10 min. The flask was then placed on ice bath and the mixture was stirred at 0C for 45 min (the triflate formation was complete in less than 30 min by TLC). The resulting pink reaction mixture was added dropwise over 5 min into a vigorously stirred 7M anh. ammonia in methanol 200mL cooled to 0C on ice bath. (Additional dichloromethane 2x10mL was used to wash the flask and syringe). The reaction flask was then placed on ambient bath and the mixture was stirred for 6 hours in a capped flask. The mixture was evaporated to dryness, the residue was made basic with K2CO3 solution in water (6g in 100mL) and the mixture was extracted twice with ether (2x200mL). Without any further washing, the combined extracts were dried (MgSO4) and evaporated. The residue was dried on highvac to remove lutidine. The crude product was purified on a column of silica 125g in a mixture chloroform-methanol-conc. aq. ammonia 100:10:1. (1.5L). The purified product was dried on higvac. Y=1.777g (90%) of a colorless oil that eventualy solidified into white hygroscopic crystals.

1H(d6-DMSO, 400MHz): 4.167(m, 1H), 3.741(m, 1H), 2.484(m, 2H), 2.348(ddABX, 15.2Hz, 5.1Hz, 1H), 2.201(ddABX, 15.0Hz, 7.8Hz, 1H), 1.533(br d, 12.5Hz, 1H), 1.373(s, 9H), 1.363(s, 3H), 1.250(br s, 2H), 1.223(s, 3H)

The intermediate triflate ester can be isolated in a nearly quantitative yield by pouring the reaction mix onto a column of silica in dichloromethane, eluting with straight dichloromethane and collecting the pink-colored band. But one has to work rather quickly and add few drops of lutidine (as a stabiliser) to all product fractions – because the neat triflate has an unpleasant tendency to suddenly self-destruct at room temp and this readily happens even in dichloromethane solution. So it is much easier to work with it without purification. 


  1. Useless!

    Where’s the morpholine?

    Comment by kinasepro — October 5, 2006 @ 12:57 am

  2. Lately we switched from morpholines to these hydroxy aminoacid pieces and they were pretty useless :). I wish we were doing morpholines instead.

    Comment by milkshake — October 5, 2006 @ 1:06 am

  3. would using ammonia treated silica gel or CHCl3 (saturated with NH3) obviate the use of aq. ammonia in your column chromatography?

    Comment by sks — October 5, 2006 @ 5:47 pm

  4. I don’t know – but I had a good experience with chloroform-methanol-ammonia mixtures for purifying amines and other polar tailing stuff on silica. I will write a new post on this topic. Thank you for asking.

    Comment by milkshake — October 5, 2006 @ 6:04 pm

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