Disclosed is a preparation method for preparing diphenylmethane diisocyanate. The preparation method comprises: under a catalyst condition, performing a pyrolysis reaction on diphenylmethane dicarbamate in an inert solvent having a boiling point lower than that of diphenylmethane diisocyanate to obtain diphenylmethane diisocyanate.

Disclosed is a preparation method for preparing diphenylmethane diisocyanate. The preparation method comprises: under a catalyst condition, performing a pyrolysis reaction on diphenylmethane dicarbamate in an inert solvent having a boiling point lower than that of diphenylmethane diisocyanate to obtain diphenylmethane diisocyanate.

The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2′-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1′-biphenyl]-3-yl carbamate to (S)-2′-chloro-1-isocyanato-6-methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl.

##STR00001##

The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2′-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1′-biphenyl]-3-yl carbamate to (S)-2′-chloro-1-isocyanato-6-methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl.

##STR00001##

The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2′-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1′-biphenyl]-3-yl carbamate to (S)-2′-chloro-1-isocyanato-6-methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl.

##STR00001##

The present invention provides a method for producing a carbamate that includes a step (1) and a step (2) described below: (1) a step of producing a compound (A) having a urea linkage, using an organic primary amine having at least one primary amino group per molecule and at least one compound selected from among carbon dioxide and carbonic acid derivatives, at a temperature lower than the thermal dissociation temperature of the urea linkage; and (2) a step of reacting the compound (A) with a carbonate ester to produce a carbamate.

The present invention provides a method for producing a carbamate that includes a step (1) and a step (2) described below: (1) a step of producing a compound (A) having a urea linkage, using an organic primary amine having at least one primary amino group per molecule and at least one compound selected from among carbon dioxide and carbonic acid derivatives, at a temperature lower than the thermal dissociation temperature of the urea linkage; and (2) a step of reacting the compound (A) with a carbonate ester to produce a carbamate.

The present invention provides a method for producing a carbamate that includes a step (1) and a step (2) described below: (1) a step of producing a compound (A) having a urea linkage, using an organic primary amine having at least one primary amino group per molecule and at least one compound selected from among carbon dioxide and carbonic acid derivatives, at a temperature lower than the thermal dissociation temperature of the urea linkage; and (2) a step of reacting the compound (A) with a carbonate ester to produce a carbamate.

A method is provided for collecting a compound of formula (III) (in which R31 is a monovalent to trivalent organic group and n31 is an integer of 1 to 3) from a liquid phase component that is formed as a by-product in a method for producing a compound of general formula (I) (in which R11 is a monovalent to trivalent organic group and n 11 is an integer of 1 to 3), wherein the collection method contains steps (1) to (3) or steps (A) and (B), and step (4). Step (1): a step for reacting the liquid phase component with at least one active hydrogen-containing compound in a reactor. Step (2): a step for returning a condensed liquid obtained by cooling gas phase components in the reactor to the reactor. Step (3): a step for discharging gas phase components that are not condensed in the step (2) to the outside of the reactor. Step (A): a step for mixing the liquid phase component, water, and a compound of general formula (III). Step (B): a step for reacting the liquid phase component with water inside the reactor. Step (4): a step for discharging, as a liquid phase component inside the reactor, the reaction liquid containing the compound of general formula (III) to the outside of the reactor.

R.sup.11NCO).sub.n11  (I)

R.sup.31NH.sub.2).sub.n31  (III)

A method is provided for collecting a compound of formula (III) (in which R31 is a monovalent to trivalent organic group and n31 is an integer of 1 to 3) from a liquid phase component that is formed as a by-product in a method for producing a compound of general formula (I) (in which R11 is a monovalent to trivalent organic group and n 11 is an integer of 1 to 3), wherein the collection method contains steps (1) to (3) or steps (A) and (B), and step (4). Step (1): a step for reacting the liquid phase component with at least one active hydrogen-containing compound in a reactor. Step (2): a step for returning a condensed liquid obtained by cooling gas phase components in the reactor to the reactor. Step (3): a step for discharging gas phase components that are not condensed in the step (2) to the outside of the reactor. Step (A): a step for mixing the liquid phase component, water, and a compound of general formula (III). Step (B): a step for reacting the liquid phase component with water inside the reactor. Step (4): a step for discharging, as a liquid phase component inside the reactor, the reaction liquid containing the compound of general formula (III) to the outside of the reactor.

R.sup.11NCO).sub.n11  (I)

R.sup.31NH.sub.2).sub.n31  (III)