907606-68-2

Usage

Uses

Used in Organic Synthesis:
(3aR,6aS)-1-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrol-2-iuM carboxyfor is used as a protecting group for amines, which is crucial for preventing unwanted reactions during the synthesis process. Its ability to protect amines allows for cleaner reactions and the synthesis of more complex organic molecules.
Used in Peptide Synthesis:
In the field of peptide synthesis, (3aR,6aS)-1-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrol-2-iuM carboxyfor serves as a reagent, facilitating the formation of peptide bonds between amino acids. This enhances the efficiency and yield of peptide synthesis, contributing to the development of novel bioactive peptides and pharmaceuticals.
Used in Pharmaceutical Research and Development:
(3aR,6aS)-1-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrol-2-iuM carboxyfor is utilized as a building block for the synthesis of various compounds in drug discovery. Its unique structure and functional groups make it a valuable component in the design and synthesis of new pharmaceutical agents, potentially leading to the development of innovative treatments for various diseases.
Used in Material Science:
In material science, (3aR,6aS)-1-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrol-2-iuM carboxyfor has potential applications in the development of new materials with unique properties. Its chemical structure and reactivity can be harnessed to create novel materials with potential uses in various industries, such as electronics, coatings, and adhesives.

Synthetic route

(1S,3aR,6aS)-2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid (S)-1,2,3,4-tetrahydro-1-naphthylammonium salt (1227704-10-0) + oxalic acid (144-62-7) + tert-butyl alcohol (75-65-0) → tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2)

Conditions

Yield

Stage #1: (1S,3aR,6aS)-2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid (S)-1,2,3,4-tetrahydro-1-naphthylammonium salt With sodium hydrogen sulfate In tert-butyl methyl ether; water for 0.5h; Stage #2: tert-butyl alcohol With dmap; sodium hydrogen sulfate; di-tert-butyl dicarbonate In tert-butyl methyl ether; water at 20 - 25℃; for 5 - 6h; Stage #3: oxalic acid With methanesulfonic acid; potassium carbonate Product distribution / selectivity; more than 3 stages;

81%

acetic acid tert-butyl ester (540-88-5) + (1R,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid hydrochloride + oxalic acid (144-62-7) → tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2)

Conditions	Yield
Stage #1: acetic acid tert-butyl ester; (1R,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid hydrochloride In dichloromethane at 0 - 21℃; Stage #2: With methanesulfonic acid In dichloromethane; water at 0 - 21℃; for 18.25h; Sealed tube; Stage #3: oxalic acid	59.7%

acetic acid tert-butyl ester (540-88-5) + (1S,3αR,6αS)-octahydrocyclopenta[c]pyrrole-1-carboxylate hydrochloride (1205676-44-3) + oxalic acid (144-62-7) → tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2)

Conditions	Yield
Stage #1: acetic acid tert-butyl ester; (1S,3αR,6αS)-octahydrocyclopenta[c]pyrrole-1-carboxylate hydrochloride With methanesulfonic acid In chloroform at 0 - 25℃; for 18h; Stage #2: oxalic acid In isopropyl alcohol at 75 - 80℃; for 0.5h;	0.08 g

(1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carbonitrile (1205676-37-4) → tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: water; hydrogenchloride / methanol / 24 h / Reflux 2.1: methanesulfonic acid / chloroform / 18 h / 0 - 25 °C 2.2: 0.5 h / 75 - 80 °C View Scheme

(1S,3aR,6aS)-di-tert-butyl hexahydrocyclo-penta[c]pyrrol-1,2(1H)-dicarboxylate (402960-06-9) → tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanesulfonic acid / tetrahydrofuran / 12 h / 22 - 27 °C / Industrial scale 2: tert-butyl methyl ether; Isopropyl acetate / 2.5 h / Industrial scale View Scheme

di-tert-butyl dicarbonate (24424-99-5) → tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: dmap / tert-butyl methyl ether; tert-butyl alcohol / 6 h / 22 - 27 °C / Industrial scale 2: methanesulfonic acid / tetrahydrofuran / 12 h / 22 - 27 °C / Industrial scale 3: tert-butyl methyl ether; Isopropyl acetate / 2.5 h / Industrial scale View Scheme

tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate (714194-68-0) + oxalic acid (144-62-7) → tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2)

Conditions	Yield
In tert-butyl methyl ether; Isopropyl acetate for 2.5h; Industrial scale;	82 kg

tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2) → tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate (714194-68-0)

Conditions	Yield
With potassium carbonate In Isopropyl acetate; water at 20 - 25℃; for 0.5 - 3h; Product distribution / selectivity;
With potassium carbonate In Isopropyl acetate; water at 20 - 25℃; for 3h; Product distribution / selectivity;
With potassium carbonate In Isopropyl acetate; water at 20℃; for 3h; Product distribution / selectivity;

tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2) → (1S,3aR,6aS)-tert-butyl 2-((S)-2-(benzyloxycarbonylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylate (926276-15-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / water; Isopropyl acetate / 3 h / 20 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / water; Isopropyl acetate / 6 h / 0 - 5 °C 2.2: 20 - 25 °C View Scheme

tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate oxalic acid salt (907606-68-2) → (1S,3aR,6aS)-tert-butyl 2-((S)-2-amino-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylate (926276-16-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / water; Isopropyl acetate / 3 h / 20 - 25 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / water; Isopropyl acetate / 6 h / 0 - 5 °C / Inert atmosphere 2.2: 20 - 25 °C 3.1: hydrogen / 10 wt% Pd(OH)2 on carbon / water; Isopropyl acetate / 1 h / 20 °C / 2311.54 Torr View Scheme
Multi-step reaction with 3 steps 1.1: potassium carbonate / water; Isopropyl acetate / 3 h / 20 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / water; Isopropyl acetate / 6 h / 0 - 5 °C 2.2: 20 - 25 °C 3.1: hydrogen / 10 wt% Pd(OH)2 on carbon / Isopropyl acetate / 1 h / 20 °C / 2311.54 Torr View Scheme

Upstream product

• 714194-68-0 tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate 
• 144-62-7 oxalic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 402960-06-9 (1S,3aR,6aS)-di-tert-butyl hexahydrocyclo-penta[c]pyrrol-1,2(1H)-dicarboxylate 
• 1205676-37-4 (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carbonitrile 
• 540-88-5 acetic acid tert-butyl ester 
• 1205676-44-3 (1S,3αR,6αS)-octahydrocyclopenta[c]pyrrole-1-carboxylate hydrochloride 
• 1227704-10-0 (1S,3aR,6aS)-2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid (S)-1,2,3,4-tetrahydro-1-naphthylammonium salt 
• 75-65-0 tert-butyl alcohol 
• 1219204-23-5 (1R,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylic acid hydrochloride 

Downstream Products

• 926276-15-5 (1S,3aR,6aS)-tert-butyl 2-((S)-2-(benzyloxycarbonylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylate 
• 714194-68-0 tert-butyl (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carboxylate 

Relevant academic research and scientific papers

PROCESS FOR PRODUCING ESTER COMPOUND

Compound (1) or a salt that is useful as an intermediate for the production of a medicine, an agrochemical or the like can be produced by a process including the following steps: (A) reacting an aldehyde (2) with nitromethane to produce a nitroaldehyde; (B) reacting the nitroaldehyde with an alcohol to produce a nitroacetal; (C) reducing the nitroacetal to produce an aminoacetal; (D) protecting an amino group in the aminoacetal to produce a protected aminoacetal; (E) treating the protected aminoacetal with an acid and subsequently with a base and then reacting the resultant product with a cyanating agent to produce a nitrile; (F) hydrolyzing the nitrile to produce a protected amino acid; and (G) substituting a group R5 in the protected amino acid by a hydrogen atom and protecting a carboxyl group therein.

Stereoselective lithiation and carboxylation of Boc-protected bicyclopyrrolidine: Synthesis of a key building block for HCV protease inhibitor telaprevir

A stereoselective process for the manufacture of bicyclopyrrolidine 7 to 2 has been developed. The process utilizes a stereoselective lithiation/carboxylation sequence. The achiral diamine ligand DPBP induces excellent diastereocontrol, and resolution with (S)-THNA provides the corresponding salt of 8 in high er and dr. Subsequent processing of 8 gives 2 as the oxalate salt in an overall yield of 27% from 7 (based on total molar charge of 7). Compound 2 was obtained with high chemical and chiral purities. The process was successfully demonstrated on >100 kg scale.

BIOCATALYTIC PROCESSES FOR THE PREPARATION OF SUBSTANTIALLY STEREOMERICALLY PURE FUSED BICYCLIC PROLINE COMPOUNDS

The present disclosure provides substantially stereomerically pure fused bicyclic proline compounds of structural Formulae II to VII as described herein, and to biocatalytic processes for their preparation, and to the enzymes used in those processes.

Processes and intermediates

The invention relates to compounds and processes useful for the preparation of protease inhibitors, particularly serine protease inhibitors. The protease inhibitors are useful for treatment of HCV infections.