Convenient and Inexpensive Synthesis of (1R,2R)‐ trans‐1‐Amino‐6‐nitroindan‐2‐ol

Abstract

Racemic trans-1-amino-6-nitroindan-2-ol (rac-1) has been prepared in five steps from inexpensive indene (7) in 96% overall yield. The key step was a direct nitration of the known trans-1-aminoindan-2-ol (rac-9) which gave sulfuric acid mono-(rac-trans-1-amino-6-nitroindan-2-yl) ester (rac-10) in quantitative yield. The latter was quantitatively converted into rac-1 by treatment with aqueous 6 N HCl and then ammonia solutions. The same transformations of (1R,2R)-9 [prepared by deracemization of rac-9 with (À)-dibenzoyl-l-tartaric acid (DBT)] proceeded without loss of the optical activity. Deracemization of rac-1 applying (þ)-(S)-l-mandelic acid (MA) furnished (1R,2R)-1 and (1S,2S)-1 in 34 and 17% yield, respectively, with e.e. ! 98 and 97.6%, respectively. Procedures for recycling of the chiral auxiliaries DBT and MA are also described. The structures of key intermediates were confirmed by X-ray crystal structure analysis.

Resolution of Praziquantel

“…99–102°C (lit. [44] 95–98°C for (–)-dibenzoyl-L-tartaric acid•H 2 O). 1 H NMR (DMSO- d 6, 200 MHz): δ = 1.03 (d, J = 6 Hz, 12H), 3.78 (sep, J = 6 Hz, 2H), 5.88 (s, 2H), 7.57–7.64 (m, 4H), 7.70–7.74 (m, 2H), 8.00–8.04 (m, 4H), 14.00 (bs, 2H) ( Figure S7 ).…”

Indene-Based Thiazolidinethione Chiral Auxiliary for Propionate and Acetate Aldol Additions

“…Oxazolidinethiones are obtained preferentially when a mild base is employed, and thiazolidinethiones can be prepared in excellent yields when a stronger base is used instead. However, when this latter method was applied to trans -amino-2-indanol 1 , thiazolidinethione 2 was obtained in poor yield. Instead, we found that the thiazolidinethione 2 was obtained in very good yield when the trans -aminoindanol 1 was first treated with sulfuric acid, and then the crude sulfated indanol was treated with potassium ethyl xanthate and aqueous sodium hydroxide and the mixture heated to 75 °C for 16 h, Scheme .…”

Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon

“…Based on our previous experience with the synthesis of indanyl nucleosides [ 7 , 9 ] and considering that 2-amino-1-indanol is not commercially available in any possible stereoisomeric form, we attempted a synthetic method that would lead to 2-amino-1-indanol with a defined cis stereochemistry and good yield. For this purpose, commercially available indene was treated with N -bromosuccinimide (NBS) to give (+/−) trans -bromohydrin 1 [ 21 , 22 ]. Thus, compound 1 was treated with ammonium hydroxide to yield a mixture of products that could not be identified; however, the treatment of compound 1 with sodium azide led to the isolation of the corresponding racemic azide 2 [ 23 ] with a very good yield ( Scheme 1 ).…”

“…lit. : 132–133 °C [ 21 , 22 ]. Compound 1 was used in the next step without any further purification.…”