[NO2]

Hi
I would need this substance (
2-(N-benzyloxycarbonyl-amino)ethyl tosylate) for a project. How would I best begin?
Based on the lack of an explanation, I'm suspecting it to be fairly straight forward.

[sjb]

Hi
I would need this substance (
2-(N-benzyloxycarbonyl-amino)ethyl tosylate) for a project. How would I best begin?
Based on the lack of an explanation, I'm suspecting it to be fairly straight forward.

OK, what are your thoughts? Is this commercially available? Any disconnects you can make?

[NO2]

I haven't seen it commercially available.
I'm thinking perhaps start with aminoethyl then tosylate it, then ...hmm

[wildfyr]

BOOM http://www.sigmaaldrich.com/catalog/product/aldrich/407909?lang=en&region=US 20 bucks for 5 grams, one step to tosylate it.

[NO2]

Wow! Thanks a lot. I didn't recognize Z or Cbz as being the the rest of the desired molecule so I kept searching for methods to get the rest done as well. I guess i can use this method to tosylate it to the OH group:
Alcohols can be converted into tosylates using tosyl chloridehttp://www.sigmaaldrich.com/catalog/product/fluka/89730?lang=de&region=AT and a base to "mop-up" the HCl by-product. http://www.chem.ucalgary.ca/courses/351/Carey5th/Ch08/ch8-10-1.html


I'm wondering if simple evaporation is adequate, or if I need some additional steps for the work-out.

I'd be using the whole thing for this here :
Synthesis of (SH2-(1-iminoethylamino)ethyll-L-homocvsteine

To liquid ammonia (130mL), cooled to -80°C (comment:apparently -35 to -40 works to), was added L-homocystine (3g), followed by sodium metal (1.06g) until the blue colour persisted for 15min. After this time N-benzyloxycarbonyl-ethanolamine tosylate (8.16g) was added and the reaction stirred at ambient temperature until the ammonia had evaporated. The residue was dissolved in water (80mL) and treated with 0.5M EDTA.sodium salt (2mL). The pH of the solution was adjusted to 7.0 with 2N sulphuric acid and the resulting white precipitate filtered off, washed with cold water and acetone and dried in a vacuum dessicator to yield the title compound as a white solid, 5.3g. Mass Spectrum M+H 313

[NO2]

Hi again
I think I'll go the pyridine route, since it seems to be the most common alcohol tosylation approach.
I've been wondering how is best go about the extraction. I've read that a aqueous-organic extraction is quite likely the right way to go, but I'm not sure how exactly to go about it (which liquids to use). Also which solvents to use for a recrystallization thereafter.

I see someone mentioned adding almost 10 times as much 2N HCl than pyridine, which, I think, causes the HCl to form a compound with the pyridine, which would then precipitate and can be filtered out leaving the desired compound in HCl. With the left over tysol chloride remain in the HCl with the product, or is that washed away as well.

If that's the nonsensical approach, then how I go about it instead?

Here would be an additional solution, which may work for the desired product as well, but I'd be looking for confirmation on that. Here's the source: http://www.orgsyn.org/Content/pdfs/procedures/CV7P0149.pdf Between page 1 and two in the PDF file.

4-Acetylpyridine oxime tosylate.
Pure E-oxime (27.1 g, 0.20 mol) and p-toluenesulfonyl chloride (47.9 g, 0.22 mol) are added to 100 mL of anhydrous pyridine in a 1-L, round-bottomed flask fitted with a drying tube and a large magnetic stirring bar. The reaction mixture is stirred at 25°C for 24 hr; a precipitate of pyridine hydrochloride forms. A 500-mL portion of ice water is added with continued stirring. the initial precipitate dissolves, and a voluminous white precipitate soon forms. This is collected by suction
filtration, washed with three 150-mL portions of cold water and dried under reduced pressure and over Drierite to constant weight. The yield of pure tosylate, mp 79–81°C, is 55.1 g (95%).

[NO2]

I guess I'll be doing it this way then. N-Boc-ethanolamine should be close enough.

http://www.rsc.org/suppdata/ob/c2/c2ob25258a/c2ob25258a.pdf
O-Tosyl-N-Boc-ethanolamine ( 2 ). 3 N-Boc-ethanolamine 1 (1.0 g, 6.2 mmol) was dissolved in DCM (5mL). Pyridine (1.3 mL) was added and the solution cooled to 0 °C. p-Toluene sulfonyl chloride (2g, 10.5 mmol) was added and the reaction stirred for 18 hours. The resultant solution was
washed with 6:1 H2O:pyridine (2 × 30 mL) and 4:1 H 2 O:37% aq. HCl (30 mL) prior to drying with Na 2 SO 4 and concentration under reduced pressure. This afforded 1.8g (92% yield) of 2 as a white amorphous solid.

I think eventually I'll make the N-Z-Ethanolamine myself with this approach:
make N-benzyloxycarbonyl-ethanolamine (N-Z-Ethanolamine ) from Benzyl chloroformate and ethylamine (much cheaper):
http://en.wikipedia.org/wiki/Benzyl_chloroformate
Benzyl chloroformate is used in organic synthesis for the introduction of the carboxybenzyl (Cbz or Z) protecting group for amines:

[Dan]

That procedure looks fine, though I'm not sure what the aqueous pyridine wash is supposed to achieve (maybe hydrolysis of the large excess of TsCl). I normally just wash with dilute HCl to remove the excess pyridine and salts. If it was me I'd probably drop it to 1.1 equiv TsCl and throw in catalytic DMAP.

[zsinger]

If you are a home chemist, good luck getting an acct. with Sigma or any other big name chem. company for that matter!
                -Zack

[NO2]

I see, thanks for that. Yes, I know, one needs a company for that. How would you do it, if that would be something you're "against", otherwise, never mind. Are there small name substitutes or something?

[NO2]

I guess I'll be doing it this way then. N-Boc-ethanolamine should be close enough.

http://www.rsc.org/suppdata/ob/c2/c2ob25258a/c2ob25258a.pdf
O-Tosyl-N-Boc-ethanolamine ( 2 ). 3 N-Boc-ethanolamine 1 (1.0 g, 6.2 mmol) was dissolved in DCM (5mL). Pyridine (1.3 mL) was added and the solution cooled to 0 °C. p-Toluene sulfonyl chloride (2g, 10.5 mmol) was added and the reaction stirred for 18 hours. The resultant solution was
washed with 6:1 H2O:pyridine (2 × 30 mL) and 4:1 H 2 O:37% aq. HCl (30 mL) prior to drying with Na 2 SO 4 and concentration under reduced pressure. This afforded 1.8g (92% yield) of 2 as a white amorphous solid.

So, I did it this way and got 3.11g instead of the expected 9g (I did 5x the amount in the example).
Something strange happend when washing it with the 4:1 H 2 O:37% aq. HCl. A tremendous amount of gas was produced, which almost made the wash impossible. I continued with an upward pointed and open stopcock, closing it for a second shaking it minimally and quickly opening it again to release the gas, which took a long time (30 sec. or so) to stop being produced (or slow down strongly).
I'm suspecting, that acidolysis of the benzoxycarbonyl group took place, producing CO2 and possibly benzyl-chloride and leaving the tosylated ethylamine. I guess only some of the product reacted, possibly leaving the 3.11g, or it is some of the other stuff.
I'll do paper chromatography to detect, if It's pure. I'll check the approximate boiling point, to see if it may be some of the unwanted products (benzyl-chloride, ethylamine-tosylate).
I've read that even 4M HCl (7.4% HCl should be less) in dioxane didn't deprotect it, but I'm suspecting that this situation may be different (the product is in dcm being washed with 5x the dcm amount of 4:1 H2O:37% HCl (aq)

I guess I need a purification method, which gets the unwanted stuff out, without using the  4:1 H 2 O:37% aq. HCl. wash. I think the unwanted stuff is HCl from the TsCl and the H from the alchohol. I guess some of the produced HCl combined with some of the pyridine to become pyridinehydrochloride, but I'm not sure if that is all I need to get out.

Thanks up front

[Dan]

Yeah, it sounds like the the Cbz hydrolysed in the acid wash. You can use much more dilute acid - its purpose is only to remove a bit of pyridine, so you can drop it down to 0.5 M (and probably even lower). Alternatively you can just remove the pyridine under vacuum if you have a good pump.

[NO2]

Thanks a lot for the info! 
Currently, I'm checking this method which I got from here http://www.orgsyn.org/Content/pdfs/procedures/CV7P0149.pdf

4-Acetylpyridine oxime tosylate.
Pure E-oxime (27.1 g, 0.20 mol) (39,0 grams of Z-ethylamine) and p-toluenesulfonyl chloride (47.9 g ( Hmm?, shouldn't be 41,94, I guess they miscalculated. 0.22 x 190.65 (TsCl molecular weight). Perhaps because it was especially pure: "p-Toluenesulfonyl chloride was purified prior to use by the procedure of L. Fieser and M. Fieser in "Reagents for Organic Synthesis.""), 0.22 mol) are added to 100 mL of anhydrous pyridine in a 1-L, round-bottomed flask fitted with a drying tube and a large magnetic
stirring bar. The reaction mixture is stirred at 25°C for 24 hr; a precipitate of pyridine hydrochloride forms. A 500mL portion of ice water is added with continued stirring. the initial precipitate dissolves, and a voluminous white precipitate soon forms. This is collected by suction filtration, washed with three 150-mL portions of cold water and dried under reduced pressure and over Drierite to constant weight. The yield of pure tosylate, mp 79–81°C, is 55.1 g (95%). "

[Dan]

Ok, but bear in mind that your product may not precipitate so easily. You might have to modify the workup.

[Doc Oc]

Just a note: the target molecule looks like something that could be used as a coupling partner to make methamphetamine.