β-Substituted γ-butyrolactams from mucochloric acid: synthesis of (±)-baclofen and other γ-aminobutyric acids and useful building blocks

Biswas, Kallolmay; Gholap, Rajesh; Srinivas, P.; Kanyal, Sachin; Sarma, Koushik Das

doi:10.1039/c3ra42201a

Cited by 11 publications

(4 citation statements)

References 29 publications

(20 reference statements)

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“…A suspension of carboxylic acid in toluene was heated to reflux for 5 h. After cooling to room temperature, the solvent was evaporated and the pure product was obtained. 1 H- and 13 C-NMR data for the compounds (±)- 2a – c [42], are identical with those described in the literature.…”

Section: Methodssupporting

confidence: 53%

Efficient Synthesis of β-Aryl-γ-lactams and Their Resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen

et al. 2015

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Abstract:An efficient synthesis of enantiomerically-pure β-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of β-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the reduction of the γ-nitroester in the presence of Raney nickel and the subsequent saponification/decarboxylation reaction. The utility of this methodology was highlighted by the preparation of enantiomerically-pure (R)-and (S)-Baclofen hydrochloride.

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Section: Methodssupporting

confidence: 53%

Efficient Synthesis of β-Aryl-γ-lactams and Their Resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen

et al. 2015

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“…The work of Das Sarma et al reported the reductive amination of mucochloric acid derivative 2.11.h with NaBH-(OAc) 3 in 50% yield (Scheme 30). 60 It should be noted that the protocol leads to racemic baclofen 2.11. The RME of the reductive amination step was 23% (379 mg of the product).…”

Section: Baclofenmentioning

confidence: 99%

Reductive Amination in the Synthesis of Pharmaceuticals

et al. 2019

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Reductive amination plays a paramount role in pharmaceutical and medicinal chemistry owing to its synthetic merits and the ubiquitous presence of amines among biologically active compounds. It is one of the key approaches to C–N bond construction due to its operational easiness and a wide toolbox of protocols. Recent studies show that at least a quarter of C–N bond-forming reactions in the pharmaceutical industry are performed via reductive amination. This Review concisely compiles information on 71 medical substances that are synthesized by reductive amination. Compounds are grouped according to the principle of action, which includes drugs affecting the central nervous system, drugs affecting the cardiovascular system, anticancer drugs, antibiotics, antiviral and antifungal medicines, drugs affecting the urinary system, drugs affecting the respiratory system, antidiabetic medications, drugs affecting the gastrointestinal tract, and drugs regulating metabolic processes. A general synthetic scheme is provided for each compound, and the description is focused on reductive amination steps. The green chemistry metric of reaction mass efficiency was calculated for all reactions.

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“…Lactam 6 can be easily transformed to N ‐substituted derivatives of 4‐hydroxy‐pyrrolidin‐2‐one. N ‐alkylation of lactam 6 by benzyl bromide furnished 8 with 82 % yield (Scheme ) . Subsequently, the dimethyl(phenyl)silyl group in 8 was converted to a hydroxy group (Scheme ) following the Tamao–Fleming oxidation with retention of configuration at C(4) chiral center and provided ( R )‐ N ‐benzyl‐4‐hydroxy‐pyrrolidin‐2‐one 9 which can be transformed to ( R )‐GABOB 10 , .…”

Section: Resultsmentioning

confidence: 99%

Organocatalyzed Diastereo‐ and Enantioselective Conjugate Addition of Nitroalkanes to β‐Silylmethylene Malonates: Direct Access to Enantioenriched Organosilanes

2020

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Cinchona-alkaloid derived bifunctional thiourea catalyzed conjugate addition reaction of nitroalkanes to -silylmethylene malonates is reported for direct access of densely functionalized enantioenriched organosilanes in good yields (up to 86 %) with excellent stereoselectivities (up to 98:2 dr and 90 % ee). Using pseudoenantiomeric catalyst, both the enantiomers of the conjugate addition products were easily accessible. Preparative scale synthesis of two conjugate addition products [a] Dr. Scheme 1. Selected state-of-the-art strategies for the synthesis of chiral organosilanes under organocatalytic conditions and present work.nitromethane to aryl/alkylidene malonates took place with moderate yields and long reaction time (3-5 days) in presence of 10 mol-% catalyst and nitromethane as a solvent. In addition, bifunctional iminophosphorane catalysed Michael addition of nitroalkanes to enone diesters is also reported. [19] However, to the best of our knowledge, organocatalytic asymmetric conjugate addition reaction of nitroalkanes to -silylmethylene malonates has not been studied so far. In this paper, we disclose the first catalytic conjugate addition of nitroalkanes including nitromethane to -silylmethylene malonates for the diastereoand enantioselective synthesis of chiral organosilanes (Scheme 1 E). The important feature of these conjugate addition products is the presence of different functional groups which could be useful for downstream synthetic transformation. Results and DiscussionInitially, we started the optimization studies by screening readily available bifunctional hydrogen-bonding organocatalysts [20] I-XII (Figure 2) for the Michael addition reaction betweensilylmethylene malonate1a and nitromethane 2a in toluene as a solvent. To our delight, quinidine derived thiourea catalyst I Eur. 2964 and good enantioselectivities (80-90 % ee) ( Table 2). Thesilylmethylene malonate 1e with the bulky tert-butyldiphenylsilyl group also participated in the conjugate addition reaction in presence of 20 mol-% of catalyst VI at room temperature and

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β-Substituted γ-butyrolactams from mucochloric acid: synthesis of (±)-baclofen and other γ-aminobutyric acids and useful building blocks

Cited by 11 publications

References 29 publications

Efficient Synthesis of β-Aryl-γ-lactams and Their Resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen

Efficient Synthesis of β-Aryl-γ-lactams and Their Resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen

Reductive Amination in the Synthesis of Pharmaceuticals

Organocatalyzed Diastereo‐ and Enantioselective Conjugate Addition of Nitroalkanes to β‐Silylmethylene Malonates: Direct Access to Enantioenriched Organosilanes

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