US 9,809,596 B1
Method for preparation of fluoro, chloro and fluorochloro alkylated compounds by homogeneous catalysis
Christoph Taeschler, Visp (CH); Florencio Zaragoza Doerwald, Visp (CH); Stefan Ellinger, Visp (CH); Matthias Beller, Nienhagen (DE); Helfried Neumann, Rostock (DE); Lin He, Rostock (DE); and Kishore Natte, Rostock (DE)
Assigned to Lonza Ltd., Visp (CH)
Appl. No. 15/522,336
Filed by Lonza Ltd, Visp (CH)
PCT Filed Nov. 5, 2015, PCT No. PCT/EP2015/075763
§ 371(c)(1), (2) Date Apr. 27, 2017,
PCT Pub. No. WO2016/071425, PCT Pub. Date May 12, 2016.
Claims priority of provisional application 62/076,618, filed on Nov. 7, 2014.
Claims priority of application No. 14192280 (EP), filed on Nov. 7, 2014; application No. 15181003 (EP), filed on Aug. 13, 2015; and application No. 15181019 (EP), filed on Aug. 14, 2015.
Int. Cl. C07D 473/10 (2006.01); C07C 41/30 (2006.01); C07C 17/272 (2006.01); C07C 45/68 (2006.01); C07D 209/10 (2006.01); C07D 207/33 (2006.01); C07D 333/12 (2006.01); C07D 207/333 (2006.01)
CPC C07D 473/10 (2013.01) [C07C 17/272 (2013.01); C07C 41/30 (2013.01); C07C 45/68 (2013.01); C07D 207/33 (2013.01); C07D 207/333 (2013.01); C07D 209/10 (2013.01); C07D 333/12 (2013.01)] 13 Claims
 
1. A method for the preparation of a fluoro, chloro or fluorochloro alkylated compound by a reaction of a compound COMPSUBST with a compound FCLALKYLHALIDE by homogeneous catalysis using a catalyst CAT
in the presence of BuPAd2 and
in the presence of TEMPO and
in the presence of a compound BAS,
BAS is selected from the group consisting of Cs2CO3, CsHCO3, NEt3, and mixtures thereof;
FCLALKYLHALIDE is a compound of formula (III);
R3—X   (III)
X is Cl, Br or I;
R3 is C1-20 alkyl or a C1-20 alkyl, wherein in the alkyl chain at least one of the hydrogens is substituted by F or Cl;
CAT is selected from the group consisting of Pd(OAc)2, Pd(TFA)2, and mixtures thereof;
COMPSUBST is selected from the group consisting of a compound COMPSUBST-I, ethene, cyclohexene, ethine, and polystyrene;
the ethene and the cyclohexene being unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of C1-10 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, N(R10)R11, CN, NO, NO2, F, Cl, Br, I, CF3, (CH2)m—C(O)Y1, S(O)2R50, CH═C(H)R28, C≡C—R24, benzyl, phenyl, naphthyl and morpholine;
the ethine being unsubstituted or substituted by 1 substituent selected from the group consisting of C1-10 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, N(R10)R11, CN, NO, NO2, F, Cl, Br, I, CF3, (CH2)m—C(O)Y1, S(O)2R50, CH═C(H)R28, C≡C—R24, benzyl, phenyl and naphthyl;
COMPSUBST-1 contains a ring RINGA;
RINGA is an unsaturated or aromatic, 5 or 6 membered carbocyclic or heterocyclic ring,
when RINGA is a heterocyclic ring, then RINGA has 1, 2 or 3 identical or different endocyclic heteroatoms independently from each other selected from the group consisting of N, O and S,
when RINGA is a 5 membered ring, then RINGA is unsubstituted or substituted by 1, 2, 3 or 4 identical or different substituents,
when RINGA is a 6 membered ring then RINGA is unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or different substituents,
any of said substituents of RINGA is independently from any other of said substituent of RINGA selected from the group consisting of C1-10 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, OH, N(R10)R11, CN, NH—OH, NO, NO2, F, Cl, Br, I, CF3, (CH2)m—C(O)Y1, S(O)2R50, CH═C(H)R28, C═C—R24, benzyl, phenyl and naphthyl;
RINGA can be condensed with a ring RINGB, RINGB is a 5 or 6 membered carbocyclic or heterocyclic ring,
when RINGB is a heterocyclic ring, is contains 1, 2 or 3 identical or different endocyclic heteroatoms independently from each other selected from the group consisting of N, O and S;
RINGB is unsubstituted or substituted with 1, 2 or 3 in case of RINGB being a 5 membered ring, with 1, 2, 3 or 4 in case of RINGB being a 6 membered ring, identical or different substituents independently from each other selected from the group consisting of C1-10 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, OH, N(R17)R18, CN, NH—OH, NO, NO2, F, Cl, Br, I, CF3, (CH2)n—C(O)Y2, S(O)2R51, CH═C(H)R38, C≡C-R34 benzyl, phenyl and naphthyl;
any of said C1-10 alkyl substituent of RINGA or RINGB is unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, OH, O—C(O)—C1-5 alkyl, O—C1-10 alkyl, S—C1-10 alkyl, S(O)—C1-10 alkyl, S(O2)-C1-10 alkyl, O—C1-6 alkylen-O—C1-6 alkyl, C3-8 cycloalkyl and 1,2,4-triazolyl;
any of said benzyl, phenyl and naphthyl substituent of RINGA or RINGB is independently from each other unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, C1-4 alkoxy, NO2 and CN;
m, n and q are identical or different and independently from each other 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
Y1, Y2 and R13 are identical or different and independently from each other selected from the group consisting of H, OH, C(R14)(R15)R16, C1-6 alkyl, O—C1-6 alkyl, phenyl, benzyl, O-phenyl, O—C1-6 alkylen-O—C1-6 alkyl and N(R19)R20;
R14, R15 and R16 are identical or different and independently from each other selected from the group consisting of H, F, Cl and Br;
R10, R11, R17, R18, R19 and R20 are identical or different and are independently from each other H or C1-6 alkyl, or R10 and R11, R17 and R18 or R19 and R20 represent together a tetramethylene or a pentamethylene chain;
R50 and R51 are identical or different and independently from each other selected from the group consisting of OH, C1-6 alkyl and C1-6 alkoxy;
R24, R34, R28 and R38 are identical or different and independently from each other selected from the group consisting of H, C1-10 alkyl, C(R25)(R26)—O—R27;
R25, R26 and R27 are identical or different and independently from each other selected from the group consisting of H and C1-10 alkyl.