Recent advances in in situ measurement technology and automation of batch crystallizers have enabled the development of batch crystallization recipes in which the desired supersaturation profile is followed by feedback control. This paper describes a new approach for following supersaturation setpoints for antisolvent crystallizations that is easy to implement for the tried crystallization. Simulations and application to a proprietary drug compound demonstrate how this combination of automation and in process measurements enables the rapid development of batch crystallization processes in the pharmaceutical industry.

In situ Raman spectroscopy was used to determine the rate of polymorph turnover for MK-A, a multipolymorphic compound in development at Merck Research Laboratories. The known crystal forms of MK-A include four anhydrous polymorphs, two hydrates, and numerous solvates. The penultimate and pure steps of this process involve a coupling reaction to generate a mixture of crystal forms followed by turnover to the desired polymorph, form A. This paper summarizes experiments to measure the kinetics of polymorph turnover from all relevant MK-A crystal forms to form A. Additionally, the turnover kinetics for polymorph reversion from form A to undesired forms were measured under simulated process upset conditions. The use of thermodynamic data to establish process boundaries and kinetic data to establish process time cycles resulted in the definition of a highly robust, cycle time efficient slurry turnover process to produce form A from any combination of other MK-A crystal forms.

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We investigate the electromechanical side instability and the stable travel range of comb-drive actuators. The stable travel range depends on the finger gap spacing, the initial finger overlap, and the spring stiffness ratio of the compliant suspension. Proper design of the suspension structure is the most effective way to stabilize the actuator and therefore to achieve a large deflection. In this paper, we propose an improved suspension design, the so-called tilted folded-beam suspension. Using such suspension, the stability of the comb-drive actuator is improved and the stable travel range is enhanced. We give the expressions for the spring constants of the proposed suspension, both in the stroke direction and perpendicular to it. The suspension designs are also studied numerically using the finite element method (FEM), in which the geometric nonlinearities, such as large deflections and stress stiffening, are considered. Analytical calculations and FEM simulations are compared. The results demonstrate that an enhanced stable travel range, compared to that of a comb-drive actuator with the most commonly used folded-beam flexure, can be achieved by using the proposed suspension design. Comb-drive actuators with various tilted folded-beam suspensions have also been fabricated using the standard surface micromachining technology and their operational performances have been characterized. The experimental results are in good agreement with the theoretical predictions.

A comprehensive study of the enantioselective Pd-catalyzed α-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et(2)O at -78 °C, transmetalation with ZnCl(2) and Negishi coupling using Pd(OAc)(2), t-Bu(3)P-HBF(4) and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation-Negishi coupling reaction; extension to a wide range of heteroaromatic bromides; total synthesis of (R)-crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and examples of α-vinylation of N-Boc pyrrolidine using vinyl bromides exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus establishing its configuration as (R)). In this way, the full scope and limitations of the methodology are delineated.

The surface-enhanced infrared absorption (SEIRA) technique has been focusing on the metallic resonator structures for decades, exploring different approaches to enhance sensitivity. Although the high enhancement is achieved, the dissipative loss and strong heating are the intrinsic drawbacks of metals. Recently, the dielectric platform has emerged as a promising alternative. In this work, we report a guided resonance-based all-dielectric photonic crystal slab as the platform for SEIRA. The guided resonance-induced enhancement in the effective path length and electric field, together with gas enrichment polymer coating, leads to a detection limit of 20 ppm in carbon dioxide (CO2) sensing. This work explores the feasibility to apply low loss all-dielectric structures as a surface enhancement method in the transmission mode.

Optical-phased arrays (OPAs) enable complex beamforming, random-access beam pointing, and simultaneous scan and tracking of multiple targets by controlling the phases of two-dimensional (2D) coherent emitters. So far, no OPA can achieve all desirable features including large 2D arrays, high optical efficiency, wideband operation in wavelengths, fast response time, and large steering angles at the same time. Here, we report on a large-scale 2D OPA with novel microelectro-mechanical-system (MEMS)-actuated phase shifters. Wavelength-independent phase shifts are realized by physically moving a grating element in the lateral direction. The OPA has 160 × 160 independent phase shifters across an aperture of 3.1 mm × 3.2 mm. It has a measured beam divergence of 0.042°× 0.031°, a field of view (FOV) of 6.6°× 4.4°, and a response time of 5.7 μs. It is capable of providing about 25,600 rapidly steerable spots within its FOV. The grating phase shifters are optimized for the near-infrared telecom wavelength bands from 1200 to 1700 nm with 85% optical efficiency.

Chiral amide 1 (MK-0364, taranabant) is a potent, selective, and orally bioavailable cannabinoid-1 receptor (CB-1R) inverse agonist indicated for the treatment of obesity. An asymmetric synthesis featuring a dynamic kinetic resolution via hydrogenation for the preparation of the bromo alcohol 5 is disclosed. Conversion of the alcohol intermediate to the chiral amide 1 is accomplished in good overall yield.