The present invention provides continuous flow processes for the preparation of the compound of Formula (2-A), an intermediate used in the preparation of zuclomiphene or a salt thereof. ##STR00001##

The present invention provides continuous flow processes for the preparation of the compound of Formula (2-A), an intermediate used in the preparation of zuclomiphene or a salt thereof. ##STR00001##

The present application discloses a 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-based phosphine ligand, an intermediate, a preparation method and uses thereof. The compound of phosphine ligand is a compound having a structure represented by formula I or formula II, or an enantiomer, a raceme, or diastereomer thereof. The phosphine ligand can be prepared via a preparation scheme in which the cheap and easily available 6,6′-dihydroxyl-3,3,3′,3′-tetramethyl-1,1′-spirobiindane is used as a raw material and the compound represented by formula III serves as the key intermediate. The new phosphine ligand developed by the present application can be used in catalytic organic reaction, in particular as a chiral phosphine ligand that is widely used in many asymmetric catalytic reactions including asymmetric hydrogenation and asymmetric allyl alkylation, and thus it has economic practicability and industrial application prospect. ##STR00001##

The present application discloses a 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-based phosphine ligand, an intermediate, a preparation method and uses thereof. The compound of phosphine ligand is a compound having a structure represented by formula I or formula II, or an enantiomer, a raceme, or diastereomer thereof. The phosphine ligand can be prepared via a preparation scheme in which the cheap and easily available 6,6′-dihydroxyl-3,3,3′,3′-tetramethyl-1,1′-spirobiindane is used as a raw material and the compound represented by formula III serves as the key intermediate. The new phosphine ligand developed by the present application can be used in catalytic organic reaction, in particular as a chiral phosphine ligand that is widely used in many asymmetric catalytic reactions including asymmetric hydrogenation and asymmetric allyl alkylation, and thus it has economic practicability and industrial application prospect. ##STR00001##

Disclosed herein is a novel process for preparing Compound A free base, 5-((2,4-diaminopyrimidin-5-yl)oxy)-4-iso-propyl-2-methoxybenzenesulfonamide, and a citrate salt of Compound A with simplified chemistry and a high overall yield: Compound A. In one embodiment, the overall yield from the starting material 2-isopropylphenol to Compound A citrate salt is greater than 50%. In another embodiment, the overall yield is greater than 60%. Also disclosed herein are novel salts and solvates of Compound A.

Disclosed herein is a novel process for preparing Compound A free base, 5-((2,4-diaminopyrimidin-5-yl)oxy)-4-iso-propyl-2-methoxybenzenesulfonamide, and a citrate salt of Compound A with simplified chemistry and a high overall yield: Compound A. In one embodiment, the overall yield from the starting material 2-isopropylphenol to Compound A citrate salt is greater than 50%. In another embodiment, the overall yield is greater than 60%. Also disclosed herein are novel salts and solvates of Compound A.

An object of the present invention is to provide a novel method for producing a fluorine-containing methylene compound. The above object can be achieved by a method for producing a compound represented by formula (1): ##STR00001##
wherein R.sup.1 represents an organic group, R.sup.A represents hydrogen or fluorine, R.sup.4a represents hydrogen or an organic group, R.sup.4b represents hydrogen or an organic group, R.sup.5a represents hydrogen or an organic group, R.sup.5b represents hydrogen or an organic group, and
R.sup.2 represents hydrogen or an organic group; R.sup.2 is optionally connected to R.sup.4a to form a ring; the method comprising step A of reacting a compound represented by formula (2): ##STR00002##
wherein X.sup.1 represents a leaving group, and other symbols are as defined above, with a compound represented by formula (3): ##STR00003##
wherein X.sup.2 represents a leaving group, and other symbols are as defined above, in the presence of a reducing agent as desired, under light irradiation.

An object of the present invention is to provide a novel method for producing a fluorine-containing methylene compound. The above object can be achieved by a method for producing a compound represented by formula (1): ##STR00001##
wherein R.sup.1 represents an organic group, R.sup.A represents hydrogen or fluorine, R.sup.4a represents hydrogen or an organic group, R.sup.4b represents hydrogen or an organic group, R.sup.5a represents hydrogen or an organic group, R.sup.5b represents hydrogen or an organic group, and
R.sup.2 represents hydrogen or an organic group; R.sup.2 is optionally connected to R.sup.4a to form a ring; the method comprising step A of reacting a compound represented by formula (2): ##STR00002##
wherein X.sup.1 represents a leaving group, and other symbols are as defined above, with a compound represented by formula (3): ##STR00003##
wherein X.sup.2 represents a leaving group, and other symbols are as defined above, in the presence of a reducing agent as desired, under light irradiation.

Provided is a compound having one or more halogens and an unsaturated double bond. Provided is a method for producing an iodine-containing vinyl monomer comprising: a) a step of providing an iodine-containing alcohol substrate having a general structure represented by the formula (1-1):

##STR00001##

(the definitions of the variables in the formula (1-1) are as described in the specification); and b) a step of dehydrating the iodine-containing alcohol substrate to obtain the iodine-containing vinyl monomer having a general structure represented by the formula (1):

##STR00002##

(the definitions of the variables in the formula (1) are as described in the specification).

An object of the present invention is to provide a novel method for producing a fluorine-containing methylene compound.

The above object can be achieved by a method for producing a compound represented by formula (1):

##STR00001## wherein R.sup.1 represents an organic group, R.sup.A represents hydrogen or fluorine, R.sup.4a represents hydrogen or an organic group, R.sup.4b represents hydrogen or an organic group, R.sup.5a represents hydrogen or an organic group, R.sup.5b represents hydrogen or an organic group, and R.sup.2 represents hydrogen or an organic group; R.sup.2 is optionally connected to R.sup.4a to form a ring; the method comprising step A of reacting a compound represented by formula (2):

##STR00002## wherein X.sup.1 represents a leaving group, and other symbols are as defined above, with a compound represented by formula (3):

##STR00003## wherein X.sup.2 represents a leaving group, and other symbols are as defined above, in the presence of a reducing agent as desired, under light irradiation.