Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

Disclosed embodiments relate to improved methods for the synthesis of activated fumarate intermediates and their use in chemical synthesis. Disclosed embodiments describe the synthesis of activated fumarate esters including those derived from activating groups including: 4-nitrophenyl, diphenylphophoryl azide, pivaloyl chloride, chlorosulfonyl isocyanate, p-nitrophenol, MEF, trifluoroacetyl and chlorine, for example, ethyl fumaroyl chloride and the subsequent use of the activated ester in situ. Further embodiments describe the improved synthesis of substituted aminoalkyl-diketopiperazines from unisolated and unpurified intermediates allowing for improved yields and reactor throughput.

The present invention provides a process for purifying a monoterpene or sesquiterpene having a purity greater than about 98.5% (w/w). The process comprises the steps of derivatizing the monoterpene (or sesquiterpene) to produce a monoterpene (or sesquiterpene) derivative, separating the monoterpene (or sesquiterpene) derivative, and releasing the monoterpene (or sesquiterpene) from the derivative. Also encompassed by the scope of the present invention is a pharmaceutical composition comprising a monoterpene (or sesquiterpene) having a purity greater than about 98.5% (w/w). The purified monoterpene can be used to treat a disease such as cancer. The present monoterpene (or sesquiterpene) may be administered alone, or may be co-administered with radiation or other therapeutic agents, such as chemotherapeutic agents.

The present invention provides a process for purifying a monoterpene or sesquiterpene having a purity greater than about 98.5% (w/w). The process comprises the steps of derivatizing the monoterpene (or sesquiterpene) to produce a monoterpene (or sesquiterpene) derivative, separating the monoterpene (or sesquiterpene) derivative, and releasing the monoterpene (or sesquiterpene) from the derivative. Also encompassed by the scope of the present invention is a pharmaceutical composition comprising a monoterpene (or sesquiterpene) having a purity greater than about 98.5% (w/w). The purified monoterpene can be used to treat a disease such as cancer. The present monoterpene (or sesquiterpene) may be administered alone, or may be co-administered with radiation or other therapeutic agents, such as chemotherapeutic agents.

The present invention provides a process for purifying a monoterpene or sesquiterpene having a purity greater than about 98.5% (w/w). The process comprises the steps of derivatizing the monoterpene (or sesquiterpene) to produce a monoterpene (or sesquiterpene) derivative, separating the monoterpene (or sesquiterpene) derivative, and releasing the monoterpene (or sesquiterpene) from the derivative. Also encompassed by the scope of the present invention is a pharmaceutical composition comprising a monoterpene (or sesquiterpene) having a purity greater than about 98.5% (w/w). The purified monoterpene can be used to treat a disease such as cancer. The present monoterpene (or sesquiterpene) may be administered alone, or may be co-administered with radiation or other therapeutic agents, such as chemotherapeutic agents.

The present invention involves a mechanochemical process in which at least two reactants are mixed without an additional solvent to produce an SNAr reaction product. In one embodiment, the mixing is achieved using a twin-screw extruder. In another embodiment, the mixing is achieved using dry mixing equipment. In one embodiment, the dry mixing equipment is selected from the group consisting of batch Paddle Mills, continuous Paddle Mills, V-Blenders, Twin Cone Blenders and Ribbon Blenders. In another embodiment, the mixing is achieved using a Fluidized Bed reactor.

The present invention involves a mechanochemical process in which at least two reactants are mixed without an additional solvent to produce an SNAr reaction product. In one embodiment, the mixing is achieved using a twin-screw extruder. In another embodiment, the mixing is achieved using dry mixing equipment. In one embodiment, the dry mixing equipment is selected from the group consisting of batch Paddle Mills, continuous Paddle Mills, V-Blenders, Twin Cone Blenders and Ribbon Blenders. In another embodiment, the mixing is achieved using a Fluidized Bed reactor.

The present invention involves a mechanochemical process in which at least two reactants are mixed without an additional solvent to produce an SNAr reaction product. In one embodiment, the mixing is achieved using a twin-screw extruder. In another embodiment, the mixing is achieved using dry mixing equipment. In one embodiment, the dry mixing equipment is selected from the group consisting of batch Paddle Mills, continuous Paddle Mills, V-Blenders, Twin Cone Blenders and Ribbon Blenders. In another embodiment, the mixing is achieved using a Fluidized Bed reactor.

The present invention relates to a process for the preparation of 1-[4-nitro-2-(trifluoromethyl)-phenyl]-alkanones and substituted phenoxyphenyl ketones.

The present invention relates to a process for the preparation of 1-[4-nitro-2-(trifluoromethyl)-phenyl]-alkanones and substituted phenoxyphenyl ketones.