3886-70-2

Basic information

• Product Name: (R)-(+)-1-(1-Naphthyl)ethylamine
• Synonyms: (R) 1-(1-NAPTHYL)ETHYLAMINE;(R)-(+)-1-(1-NAPHTHYL)ETHYLAMINE;(R)-1-(1-NAPHTHYL)ETHYLAMINE;(R)-1-(NAPHTHALEN-1-YL)ETHANAMINE;(R)-(+)-1-(NAPHTHYL)ETHYLAMINE;(R)-(+)-A-(1-NAPHTHYL)ETHYLAMINE;(R)-(+)-ALPHA-(1-AMINOETHYL)NAPHTHALENE;(R)-(+)-ALPHA-(1-NAPHTHYL)ETHYLAMINE
• CAS NO: 3886-70-2
• Molecular Formula: C₁₂H₁₃N
• Molecular Weight: 171.24
• EINECS: 223-425-5
• Product Categories: chiral;Amines (Chiral);Analytical Chemistry;Chiral Building Blocks;e.e. / Absolute Configuration Determination (NMR);Enantiomer Excess & Absolute Configuration Determination;for Resolution of Acids;Optical Resolution;Synthetic Organic Chemistry;Miscellaneous;Cinacalcet Intermediate
• Mol File: 3886-70-2.mol

Chemical Properties

• Melting Point: 135-136 °C
• Boiling Point: 153 °C11 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: brown/Liquid
• Density: 1.067 g/mL at 20 °C(lit.)
• Vapor Pressure: 0.00214mmHg at 25°C
• Refractive Index: n20/D 1.623(lit.)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Ethanol (Slightly), Methanol (Slightly)
• PKA: 9.26±0.40(Predicted)
• Water Solubility: Soluble in water (<10/l).
• Sensitive: Air Sensitive
• Stability: Stable. Air-sensitive. Incompatible with acids, oxidizing agents, acid anhydrides, chloroformates, acid chlorides.
• BRN: 2208025
• CAS DataBase Reference: (R)-(+)-1-(1-Naphthyl)ethylamine(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-(+)-1-(1-Naphthyl)ethylamine(3886-70-2)
• EPA Substance Registry System: (R)-(+)-1-(1-Naphthyl)ethylamine(3886-70-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RIDADR: 2735
• WGK Germany: 3
• RTECS: QJ6963000
• F: 10-34
• TSCA: Yes
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 3886-70-2(Hazardous Substances Data)

Usage

Uses

Used in Chiral Synthesis:
(R)-(+)-1-(1-Naphthyl)ethylamine is used as a chiral auxiliary in organic reactions for the synthesis of β-amino acids. Its presence helps in controlling the stereochemistry of the reaction, leading to the formation of enantiomerically pure products. This is particularly important in the pharmaceutical industry, where the stereochemistry of a drug can significantly affect its efficacy and safety.
Used in Enantioselective Transformations:
In the field of organic chemistry, (R)-(+)-1-(1-Naphthyl)ethylamine is also used in the enantioselective transformation of ketones to nitroolefins. This reaction is crucial for the synthesis of various biologically active compounds and pharmaceuticals, as it allows for the preparation of enantiomerically pure compounds with a high level of selectivity.
Used in Determination of Absolute Configuration:
(R)-(+)-1-(1-Naphthyl)ethylamine finds application in the determination of the absolute configuration of primary amines. It is used in conjunction with chiral (2-nitrophenyl)proline amides and H NMR spectroscopy to accurately determine the stereochemistry of primary amines. This technique is valuable in the field of stereochemistry and drug development, as it allows for the unambiguous assignment of the absolute configuration of chiral centers in molecules.

InChI:InChI=1/C12H13N/c1-9(13)11-8-4-6-10-5-2-3-7-12(10)11/h2-9H,13H2,1H3/p+1/t9-/m1/s1

Upstream product

• 42882-31-5 (RS)-1-(1-naphthyl)ethylamine 
• 371-27-7 2,2,2-trifluoroethylbutyrate 
• 121328-40-3 (S)-4-Isopropyl-3-((R)-1-naphthalen-1-yl-ethyl)-oxazolidin-2-one 
• 74629-94-0 (1S,2R,R)-cis-1-(2-Hydroxy-1,2,3,4-tetrahydro-1-naphthyl)methyl N-<1-(1-naphthyl)ethyl>amide 
• 74629-96-2 (1S,2S,R)-trans-1-(2-Hydroxy-1,2,3,4-tetrahydro-1-naphthyl)methyl N-<1-(1-naphthyl)ethyl>amide 
• 74629-97-3 (1R,2R,R)-trans-1-(2-Hydroxy-1,2,3,4-tetrahydro-1-naphthyl)methyl N-<1-(1-Naphthyl)ethyl>amide 
• 74629-95-1 (1R,2S,R)-cis-1-(2-Hydroxy-1,2,3,4-tetrahydro-1-naphthyl)methyl N-<1-(1-naphthyl)ethyl>amide 
• 54279-03-7 methyl 1-naphthyl ketone O-methyloxime 
• 141-78-6 ethyl acetate 
• 941-98-0 1'-naphthacetophenone 
• 498542-91-9 (1S,2S)-N-acetyl-1,2-bis(trifluoromethanesulfonamido) cyclohexane 
• 123-66-0 Ethyl hexanoate 
• 106-33-2 ethyl laurate 
• 10420-89-0 (S)-1-(1-Naphthyl)ethylamine 

Downstream Products

• 64187-98-0 (1R,2'S)-N-<1-(1-naphthyl)ethyl>-2-phenylbutanamide 
• 72165-50-5 (R)-3,3,3-Trifluoro-2-methoxy-2-phenyl-propionic acid 3-hydroxy-3-methyl-4-((R)-1-naphthalen-1-yl-ethylcarbamoyl)-butyl ester 
• 77732-38-8 (3S,1'R)-N-(1-naphthylethyl)-3-(4-methylphenyl)butanamide 
• 77732-39-9 (3R,1'R)-N-(1-naphthylethyl)-3-(4-methylphenyl)butanamide 
• 74629-94-0 (1S,2R,R)-cis-1-(2-Hydroxy-1,2,3,4-tetrahydro-1-naphthyl)methyl N-<1-(1-naphthyl)ethyl>amide 
• 74629-95-1 (1R,2S,R)-cis-1-(2-Hydroxy-1,2,3,4-tetrahydro-1-naphthyl)methyl N-<1-(1-naphthyl)ethyl>amide 
• 147963-59-5 Benzoic acid (S)-2-cyano-1-[((R)-1-naphthalen-1-yl-ethylcarbamoyl)-methyl]-ethyl ester 
• 87691-43-8 Boc-Phe-His-Sta-Leu-(+)-α-naphthylethylamide 
• 87691-43-8 Boc-Phe-His-Sta-Leu-(-)-α-naphthylethylamide 
• 144271-30-7 (3R,1'R)-N-(1-naphthylethyl)-3-(4-methyl-1,3-cyclohexadienyl)butanamide 
• 85642-68-8 C₁₉H₂₀NPS 
• 127106-88-1 ((R)-1-Naphthalen-1-yl-ethyl)-[2-phenyl-eth-(E)-ylidene]-amine 
• 79120-85-7 Phthalic acid mono-((R)-1-ethynyl-nonyl) ester; compound with (R)-1-naphthalen-1-yl-ethylamine 
• 79120-87-9 Phthalic acid mono-((S)-1-ethynyl-nonyl) ester; compound with (S)-1-naphthalen-1-yl-ethylamine 

Relevant articles and documents

A METHOD FOR PREPARATION OF DIASTEREOMERIC LACTATE SALTS OF 1-(1-NAPHTHYL)ETHYL AMINE AND PURE ENANTIOMERS OF 1-(1-NAPHTHYL)ETHYL AMINE

The invention relates to method for preparation of pure enantiomers of 1-(1-naphthyl)ethyl amine by preparing lactate salt with chiral lactic acid as resolving agent. The method comprises reaction of L-lactic acid or D-lactic acid with racemic 1-(1-naphthyl)ethyl amine to form diastereomeric salts of (R/S)-1-(1-naphthyl)ethyl amine-(D/L)-lactate from which pure enantiomer is isolated. The invention also comprises method for preparation of compound with enriched enantiomers of 1-(1-naphthyl)ethyl amine from the mother liquor separated from the diastereomeric lactate salt. The enriched enantiomer is reacted with pure enantiomers of mandelic acid or lactic acid, preferably D-mandelic acid or L-mandelic acid and converted to diastereomeric mandelate salt. Pure (R)- or (S)-1-(1-naphthyl)ethyl amine is obtained from the diastereomeric mandelate salt. The chiral purity of pure enantiomer obtained is between 99% and 100%.

Catalytic Reductions Without External Hydrogen Gas: Broad Scope Hydrogenations with Tetrahydroxydiboron and a Tertiary Amine

Facile reduction of aryl halides with a combination of 5% Pd/C, B2(OH)4, and 4-methylmorpholine is reported. Aryl bromides, iodides, and chlorides were efficiently reduced. Aryl dihalides containing two different halogen atoms underwent selective reduction: I over Br and Cl, and Br over Cl. Beyond these, aryl triflates were efficiently reduced. This combination was broadly general, effectuating reductions of benzylic halides and ethers, alkenes, alkynes, aldehydes, and azides, as well as for N-Cbz deprotection. A cyano group was unaffected, but a nitro group and a ketone underwent reduction to a low extent. When B2(OD)4 was used for aryl halide reduction, a significant amount of deuteriation occurred. However, H atom incorporation competed and increased in slower reactions. 4-Methylmorpholine was identified as a possible source of H atoms in this, but a combination of only 4-methylmorpholine and Pd/C did not result in reduction. Hydrogen gas has been observed to form with this reagent combination. Experiments aimed at understanding the chemistry led to the proposal of a plausible mechanism and to the identification of N,N-bis(methyl-d3)pyridin-4-amine (DMAP-d6) and B2(OD)4 as an effective combination for full aromatic deuteriation. (Figure presented.).

Enzymatic Primary Amination of Benzylic and Allylic C(sp3)-H Bonds

Aliphatic primary amines are prevalent in natural products, pharmaceuticals, and functional materials. While a plethora of processes are reported for their synthesis, methods that directly install a free amine group into C(sp3)-H bonds remain unprecedented. Here, we report a set of new-to-nature enzymes that catalyze the direct primary amination of C(sp3)-H bonds with excellent chemo-, regio-, and enantioselectivity, using a readily available hydroxylamine derivative as the nitrogen source. Directed evolution of genetically encoded cytochrome P411 enzymes (P450s whose Cys axial ligand to the heme iron has been replaced with Ser) generated variants that selectively functionalize benzylic and allylic C-H bonds, affording a broad scope of enantioenriched primary amines. This biocatalytic process is efficient and selective (up to 3930 TTN and 96percent ee), and can be performed on preparative scale.

Addition of Highly Polarized Organometallic Compounds to N-tert-Butanesulfinyl Imines in Deep Eutectic Solvents under Air: Preparation of Chiral Amines of Pharmaceutical Interest

Highly polarized organometallic compounds of s-block elements are added smoothly to chiral N-tert-butanesulfinyl imines in the biodegradable d-sorbitol/choline chloride eutectic mixture, thereby granting access to enantioenriched primary amines after quantitatively removing the sulfinyl group. The practicality of the method is further highlighted by proceeding at ambient temperature and under air, with very short reaction times (2 min), enabling the preparation of diastereoisomeric sulfinamides in very good yields (74–98 %) and with a broad substrate scope, and the possibility of scaling up the process. The method is demonstrated in the asymmetric syntheses of both the chiral amine side-chain of (R,R)-Formoterol (96 % ee) and the pharmaceutically relevant (R)-Cinacalcet (98 % ee).

Asymmetric reduction method of nitrogen-phosphonyl protected imine

The invention discloses an asymmetric reduction method of nitrogen phosphonyl protective imine. The nitrogen phosphonyl protective imine is reduced into chiral amine in a hydrogen atmosphere under theaction of a metal catalyst and alkali, and the metal catalyst is prepared from a metal iridium complex and a nitrogen-phosphorus chiral ligand. The method provided by the invention has the characteristics of high enantioselectivity, high yield and high conversion number (TON). The method can be used for synthesizing various substituted chiral amines, can be used as an important intermediate for preparing various medicines, and has important significance for industrial production of medicines.

Method for asymmetrically synthesizing (R)-cinacalcet

The invention discloses a new method for asymmetrically synthesizing (R)-cinacalcet. The method includes: taking racemic 2-bromo-propionic acid (4-methoxybenzyl) ester as a starting raw material, andbeing in asymmetric Negishi cross coupling reaction with 2-nathphyl zinc bromide under catalysis of CoI2 and chiral ligand to generate (R)-2-(1-nathphyl) propionic acid (4-methoxybenzyl) ester; beingin reaction with oxalyl chloride through LiOH reduction to generate (R)-2-(1-nathphyl) propionyl chloride; being reaction with ammonia water to generate (R)-2-(1-nathphyl) propionamide, and allowing Hofmann degradation to obtain (R)-1-nathphalene ethylamine; being in reaction with 3-(trifluoromethyl) phenylpropionic acid to generate (R)-N-(1-nathphalene ethyl)-3-(3-trifluoromethylphenyl) propionamide, and allowing LiAlH4 reduction to obtain (R)-cinacalcet. Cobalt catalyzed asymmetric Negishi cross coupling reaction is utilized for the first time to build the chiral center of (R)-cinacalcet, the method is mild in reaction condition and environment-friendly, and optical purity of (R)-cinacalcet is high (99%ee).

Enantioselective synthesis of (R)-Cinacalcet via cobalt-catalysed asymmetric Negishi cross-coupling

A novel enantioselective synthesis of (R)-cinacalcet with 99% enantiomeric excesses (ee) has been achieved. The main strategies of the approach include a gram-scale cobalt-catalysed asymmetric cross-coupling of racemic ester with arylzinc reagent, Hoffman-type rearrangement of acidamide, the amidation of chiral amine, and improving the ee of chiral amide from 87% to 99% via recrystallization.

Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2

A ruthenium/C3-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H2 as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C3-TunePhos is also presented.

Chemoenzymatic Approaches to the Synthesis of the Calcimimetic Agent Cinacalcet Employing Transaminases and Ketoreductases

Several chemoenzymatic routes have been explored for the preparation of cinacalcet, a calcimimetic agent. Transaminases (TAs) and ketoreductases (KREDs) turned out to be useful biocatalysts for the preparation of key optically active precursors. Thus, the asymmetric amination of 1-acetonaphthone yielded an enantiopure (R)-amine, which can be alkylated in one step to yield cinacalcet. Alternatively, the bioreduction of the same ketone resulted in an enantiopure (S)-alcohol, which was easily converted into the previous (R)-amine. In addition, the reduction was efficiently performed with the KRED and its cofactor co-immobilized on the same porous surface. This self-sufficient heterogeneous biocatalyst presented an accumulated total turnover number (TTN) for the cofactor of 675 after 5 consecutive operational cycles. Finally, in a preparative scale synthesis the TA-based approach was performed in aqueous medium and led to enantiopure cinacalcet in two steps and 50% overall yield. (Figure presented.).

Preparation method of chiral amine compounds

The invention discloses a preparation method of chiral amine compounds. The preparation method of the chiral amine compounds specifically comprises the following steps: adding ketone compounds and chiral auxiliary (S)-a-phenylethylamine or (R)-a-phenylethylamine to an organic solvent to prepare an imine intermediate under the action of a large-steric-hindrance boron catalyst and a water removing agent; adding a reducing agent to the imine intermediate without separation and purification, and preparing the chiral amine compounds with a one-pot method. By calculation, the product yield is 81%-96%, and the highest de value can reach 99%. Compared with the prior art, the use amount of the large-steric-hindrance boron catalyst in the method can be reduced to 0.1 mol%, use of the equivalent metal catalyst is avoided from the source, and the method has the characteristics of being simple to operate, mild in reaction condition, wide in substrate applicability, environmental friendly and the like, and has better application value and potential economic and social benefits.