13
3, A process as claimed in either claim 1 or claim 2 wherein R is ethyl.
25 2. A process as claimed in claim 1 wherein X is benzyl.
PCTIEP20H/071145
(IDa)
suspensIOn;
adding water to the suspension of step ii) to form a biphasic system
comprising an aqueous phase and an organic phase, and discarding the
aqueous phase;
adding an acid to the organic phase of step iii) to form a biphasic system
comprising an acidic aqueous phase and an organic phase, and discarding
;
the acidlc'l!iqueous phase;
v) washing the organic phase of step iv) with water.
ii)
iii)
iv)
i) providing a crude reaction product comprising said compound of formula
lIla;
adding ethyl acetate to the crude reaction product of step i) to prepare a
~NH-Y
X-O~COOR
1. A process for preparing a compound offormula IlIa:
Claims:
5
WO 2012/072567
wherein:
R denotes an alkyl group with 1 to 5 carbon' atoms;
X denotes a protecting group for an alcohol; o'
lOYd_enotes a protecting group for an amine, and
wherein the process comprises a work-up process comprising the steps of:
15
4. A process as claimed in anyone of claims 1 to 3 wherein Y is tert-butyl carbamate
30 (Boc).
20
WO 2012/072567 PCTIEP20H/071145
5. A process as claimed in anyone of claims 1 to 4 wherein in step ii) the amount of
ethyl acetate addest compared to the amount of a starting material comprising a
compound of formula lla:
5
~NH2
X-O~COOR
(lla)
wherein X and R are defined as in claim 1;
is between 15: 1 and 25: 1 in volume/weight%.
10 6. A process as claimed in anyone of claims 1 to 5 wherein in step iii) the amount of
-. .
w_ater added is about half the amount of ethyl acetate added in step ii).
7. A process a.s claimed in anyone of claims 1 to 6 wherein in step iv) the acid added
is Hei.
15
8. A process as claimed in anyone of claims 1 to 7 wherein in step iv) the washing
includes washing with pure water, with an aqueous solution of sodium hydrogen
carbonate and with brine.
20 9. A process as claiUl~d in anyone of claims 1 to 8 further including the steps of
concentrating the composition from step iv) under reduced pressure,drying and
purifying. \ ,.~
10. A process as claimed in anyone of claims 1 to 9 wherein the crude reaction
I
25 product includes a mixture of the syn- and anti-enantiomer of the compound of
formulailla.
11. A process for preparing the compound of formula V:
30
LG--.A-NHY
~COOR
(Va)
14
WO 2012/072567 PCTJEP2011/071145
wherein Y is as defined in either claim 1 or claim 4 and R is as defined in either
claim 1 or claim 3, and LG is aleaving group; ,
I '..
wherein said pro~s comprises preparing the compound offormula IUa according to
the process of anyone of claimsl-lo.
5
12. Aprocess as defined in claim 11 wherein said leaving group is a halogen
substituent or a group represented by -OR2 wherein R2 is either a tluorosulfonic acid
substituent or an aromatic sulfonic acid substituent.
10 13. Aprocess as defined in claim 12 wherein said leaving group is selected from a
toluenesulfonic acid substituent, a nitrobenienesulfonic acid substituen~ a
benzenesulfonic acid substituent, a trifluoromethanesu1fonic.acid substituent, a
fluorosulfonic acid substituent, or a perfluoroa1kylsulfonic aCid substituent.
IS 14. Aprocess as defined in either claim 11 or claim12 wherein said compound of
formula Va is Ii compound offonnuJa V:'
, ~NHBoc
TfO~COOEt
(V)
20 IS. AproCess for preparing acomPouud of formUla VI: .
-. 1 f \. '
wherein said process comprises preparing the compound of formula IlIa according to
25 the process as defined in anyone of claims'l-l 0,'
.gated this 01/05/2013
. 1-
'[SHRlMANT S GH]
OFREMFRY & AGAR
ATTORNEY FOR THE APPLI ANTtS]