US 9,809,565 B2
Formation of chiral 4-chromanones using chiral pyrrolidines in the presence of ureas or thioureas
Ulla Letinois, Basel (CH); Thomas Netscher, Basel (CH); and Stephan Ackermann, Basel (CH)
Assigned to DSM IP ASSETS B.V., Heerlen (NL)
Appl. No. 14/902,871
Filed by DSM IP ASSETS B.V., Heerlen (NL)
PCT Filed Jul. 3, 2014, PCT No. PCT/EP2014/064208
§ 371(c)(1), (2) Date Jan. 5, 2016,
PCT Pub. No. WO2015/001030, PCT Pub. Date Jan. 8, 2015.
Claims priority of application No. 13175330 (EP), filed on Jul. 5, 2013.
Prior Publication US 2016/0145228 A1, May 26, 2016
Int. Cl. C07D 311/00 (2006.01); C07D 311/22 (2006.01)
CPC C07D 311/22 (2013.01) 8 Claims
 
1. A process for the manufacturing of compound of formula (I)

OG Complex Work Unit Drawing
comprising the step of reacting a compound of formula (II-A) and a compound of formula (II-B) in the presence of at least one chiral compound of formula (II-C) and in the presence of at least one urea compound of formula (X-A) or at least one thiourea compound of formula (X-B):

OG Complex Work Unit Drawing
wherein:
R1, R3 and R4 are independently from each other hydrogen or methyl groups;
R2 and R2′ represents hydrogen or a phenol protection group;
R5 represents either a linear or branched completely saturated C6-25-alkyl group or a linear or branched C6-25-alkyl group comprising at least one carbon-carbon double bond;
Y1 represents either CH2Y2 or

OG Complex Work Unit Drawing
wherein
R6 represents a linear or branched C1-12-alkyl group which optionally further comprises at least one aromatic group and/or C═O and/or NH and/or NH2 group;
Y2 represents either OH or OR7 or NHR7 or NHCOOR7 or

OG Complex Work Unit Drawing
 and wherein
R7 represents either
a linear or branched C1-12-alkyl group which optionally further comprises at least one aromatic group and/or C═O and/or NH and/or NH2 group
or
an aryl group or a substituted aryl group or a heteroaryl group or a substituted heteroaryl group, and wherein
the dotted line represents the a bond by which the corresponding substituent is bound to the rest of formula (II-C); and wherein
the symbol * represents the chiral centre of the chiral isomer of formula (I); and
wherein
(1) Z1 represents either H or a group CH2Z4;
Z2 represents either H or a group CH2Z4;
Z3 represents either H or a group CH2Z4; wherein
Z4 represents H or an C1-C6 alkyl group; or wherein
(2) Z1, Z2 or Z3 is a group of formula (XII):

OG Complex Work Unit Drawing
 wherein
Z5 is a C1-C6 alkyl group or a CF3 group and n stands for 0, 1, 2 or 3, with the proviso that if Z1 is different from H, that Z2 represents H, and wherein the compound of formula (IIc) is selected from the group consisting of:

OG Complex Work Unit Drawing