46022-05-3

Basic information

• Product Name: (1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID
• Synonyms: (1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID;(1R,2R)-1,2-CYCLOHEXANEDICARBOXYLIC ACID;(R,R)-CYCLOHEXANE-1,2-DICARBOXYLIC ACID;(1R,2R)-(-)-trans-cyclohexane-1,2-dicar-boxylic acid;(1R,2R)-(?-trans-Cyclohexane-1,2-dicarboxylic acid;(1R 2R)-(-)-TRANS-CYCLOHEXANE-1 2-DICAR&;1,2-Cyclohexanedicarboxylic acid, (1R,2R)-;(1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID 99+%
• CAS NO: 46022-05-3
• Molecular Formula: C₈H₁₂O₄
• Molecular Weight: 172.18
• EINECS: 1308068-626-2
• Product Categories: Carboxylic Acids (Chiral);Chiral Building Blocks;Synthetic Organic Chemistry;Chiral Reagents;Miscellaneous Reagents
• Mol File: 46022-05-3.mol

Chemical Properties

• Melting Point: 184 °C
• Boiling Point: 384.075 °C at 760 mmHg
• Flash Point: 200.254 °C
• Appearance: /
• Density: 1.315 g/cm³
• Refractive Index: -18 ° (C=1, Acetone)
• Storage Temp.: Store below +30°C.
• Solubility: Soluble in acetone.
• PKA: 4.18±0.28(Predicted)
• CAS DataBase Reference: (1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: (1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID(46022-05-3)
• EPA Substance Registry System: (1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID(46022-05-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: WGK 3 highly water endangering
• Hazardous Substances Data: 46022-05-3(Hazardous Substances Data)

Usage

Uses

Used in Cyclodextrin Derivatives:
(1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID is used as a chiral dicarboxylic acid guest for the formation of cyclodextrin derivatives. It forms CD-active species when combined with other chiral dicarboxylic acids, such as Boc-L-aspartic acid. These cyclodextrin derivatives exhibit unique properties, such as chiral recognition and complexation abilities, making them valuable in various industries.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, (1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID is used as a chiral building block for the synthesis of various pharmaceutical compounds. Its unique chiral properties enable the development of enantiomerically pure drugs, which can have improved efficacy and reduced side effects compared to their racemic counterparts.
Used in Food Industry:
In the food industry, (1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID is used as a chiral additive to enhance the flavor and aroma of food products. Its ability to form inclusion complexes with various flavor compounds allows for controlled release and improved stability of these compounds in food products.
Used in Cosmetics Industry:
In the cosmetics industry, (1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID is used as a chiral ingredient for the development of skincare and fragrance products. Its complexation properties enable the encapsulation of active ingredients, improving their stability, bioavailability, and efficacy in cosmetic formulations.
Used in Environmental Applications:
(1R,2R)-(-)-1,2-CYCLOHEXANEDICARBOXYLIC ACID is used as a chiral adsorbent for the removal of pollutants from water and air. Its ability to selectively bind and remove specific contaminants makes it a valuable tool in environmental remediation efforts.

Synthetic route

(R)-1-phenyl-ethyl-amine (3886-69-9) + racemic trans-cyclohexane-1,2-dicarboxylic acid → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + C24H30N2O2

Conditions	Yield
Stage #1: (R)-1-phenyl-ethyl-amine; racemic trans-cyclohexane-1,2-dicarboxylic acid In methanol at 0 - 35℃; Inert atmosphere; Stage #2: With hydrogenchloride In water Inert atmosphere; enantioselective reaction;	A 25% B n/a

(R,R)-1,2-cyclohexane dicarboxylic acid (R)-1-phenylethyl amine salt → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
With hydrogenchloride In water	800 mg
With sodium hydroxide In chloroform; water for 0.5h; pH=10 - 11;

(x)C8H11N*C8H12O4 → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
With hydrogenchloride In water

trans-1,2-cyclohexanedicarboxylic acid (2305-32-0) → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: ethanol / 6.5 h / -70 - 20 °C / Resolution of racemate 2: hydrogenchloride / water View Scheme
With (R)-1-phenyl-ethyl-amine In methanol; isopropyl alcohol at 30 - 40℃;	29.4 g

2-(nitromethyl)cyclohexane-1-carbaldehyde → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 2: acetic acid; sodium nitrite / dimethyl sulfoxide / 8 h / 40 °C / Inert atmosphere View Scheme

(1R,2R)-2-(nitromethyl)cyclohexane-1-carboxylic acid (1292320-69-4) → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
With acetic acid; sodium nitrite In dimethyl sulfoxide at 40℃; for 8h; Inert atmosphere;

trans-cyclohex-4-ene-1,2-dicarboxylic acid (88-98-2, 2305-26-2, 15573-40-7, 50987-15-0, 51096-07-2, 51096-08-3) → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: palladium; hydrogen / methanol / 30 - 35 °C 2.1: ethanol / 30 h / 35 - 75 °C 2.2: 1 h View Scheme

(R)-1-phenyl-ethyl-amine (3886-69-9) + trans-1,2-cyclohexanedicarboxylic acid (2305-32-0) → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
Stage #1: (R)-1-phenyl-ethyl-amine; trans-1,2-cyclohexanedicarboxylic acid In ethanol at 35 - 75℃; for 30h; Stage #2: With hydrogenchloride In water; ethyl acetate for 1h;

trans-1,2-cyclohexanedicarboxylic acid (2305-32-0) → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + (1S,2S)-cyclohexane-1,2-dicarboxylic acid (610-10-6, 1687-30-5, 2305-32-0, 21963-41-7, 46022-05-3, 610-09-3)

Conditions	Yield
With FS-Hydrodex β-6TBDM column Resolution of racemate;

cyclohex-4-ene-1,2-dicarboxylic acid (88-98-2) → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogen / methanol / 20 °C / Autoclave 2: methanol / 2.5 h / 20 °C 3: sodium hydroxide / water; chloroform / 0.5 h / pH 10 - 11 View Scheme

dimethyl cis-1,2-cyclohexanedicarboxylate (1687-29-2) → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + (1S,2S)-cyclohexane-1,2-dicarboxylic acid (610-10-6, 1687-30-5, 2305-32-0, 21963-41-7, 46022-05-3, 610-09-3)

Conditions	Yield
Stage #1: dimethyl cis-1,2-cyclohexanedicarboxylate With sodium methylate In methanol for 4h; Inert atmosphere; Reflux; Stage #2: With water; sodium hydroxide at 75℃; for 4h; Inert atmosphere; Stage #3: With hydrogenchloride In water at 0 - 5℃; pH=2; Inert atmosphere; Optical yield = 16.399 %ee; diastereoselective reaction;

racemic trans-cyclohexane-1,2-dicarboxylic acid → (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3)

Conditions	Yield
With (R)-1-phenyl-ethyl-amine at 5℃; Temperature;

(1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + β-naphthol (135-19-3) → trans-(1R,2R)-cyclohexane dicarboxylic acid di(2-naphthyl)ester

Conditions	Yield
With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine	100%
With N,N-bis[2-oxo-3-oxazolidinyl]phosphorodiamidic chloride; triethylamine In dichloromethane Esterification;

methanol (67-56-1) + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → (1R,2R)-1,2-cyclohexanedicarboxylic acid dimethyl ester (140459-96-7)

Conditions	Yield
With thionyl chloride at 20℃; for 2h; Reflux;	99%
With sulfuric acid at 40℃; for 18h;	97%
With sulfuric acid at 40℃; for 24h; Cooling with ice;	91%

(1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → trans-1,2-cyclohexanedicarboxylic anhydride (85-42-7, 13149-00-3, 14166-21-3, 31982-85-1, 71749-03-6, 97233-90-4)

Conditions	Yield
With acetyl chloride	98%
With acetic anhydride at 80℃; for 1h;
With acetic anhydride at 80℃; for 1h;

(1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → (+)-(1R,2R)-trans-1,2-bis(hydroxymethyl)cyclohexane (65376-05-8)

Conditions	Yield
With sodium tetrahydroborate; iodine In tetrahydrofuran at 0℃; for 5h; Reflux;	88.4%
With Red-Al In tetrahydrofuran; toluene for 5h; Inert atmosphere; Reflux;	85.2%
Multi-step reaction with 2 steps 1: diethyl ether 2: LiAlH4 / diethyl ether View Scheme

uranyl nirate hexahydrate + cadmium(II) nitrate tetrhydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → O2U(2+)*2C8H10O4(2-)*Cd(2+)*3H2O

Conditions	Yield
In water; acetonitrile at 140℃; Autoclave; High pressure;	85%

cadmium(II) nitrate tetrhydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + trans-1,2-bis(4-pyridyl)ethylene (1135-32-6) → C8H10O4(2-)*2C12H10N2*3H2O*Cd(2+)

Conditions	Yield
In water at 140℃; for 72h; Sealed tube;	83%

diazomethane (186581-53-3, 908094-01-9) + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → (1R,2R)-1,2-cyclohexanedicarboxylic acid dimethyl ester (140459-96-7)

Conditions	Yield
In diethyl ether at 0℃; Inert atmosphere;	75%
In diethyl ether
In diethyl ether

uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → O2U(2+)*C8H10O4(2-)

Conditions	Yield
With silver nitrate In water; acetonitrile at 140℃; Reagent/catalyst; Autoclave; High pressure;	75%

(1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → (R,R)-trans-2-aminocyclohexanecarboxylic acid hydrochloride

Conditions	Yield
Stage #1: (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid With acetyl chloride Heating; Stage #2: With ammonia In dichloromethane at 20℃; Stage #3: With bis-[(trifluoroacetoxy)iodo]benzene In water; acetonitrile at 20℃; Further stages.;	74%

nickel(II) chloride hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + trans-1,2-bis(4-pyridyl)ethylene (1135-32-6) → C8H10O4(2-)*2C12H10N2*3H2O*Ni(2+)

Conditions	Yield
In water at 140℃; for 72h; Sealed tube;	73.2%

di-tert-butyl dicarbonate (24424-99-5) + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → (1R,2R)-2-((tert-butoxycarbonyl)amino)cyclohexane-1-carboxylic acid (233661-54-6)

Conditions	Yield
Multistep reaction.;	67%

cobalt(II) chloride hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + trans-1,2-bis(4-pyridyl)ethylene (1135-32-6) → Co(2+)*C8H10O4(2-)*2C12H10N2*3H2O

Conditions	Yield
In water at 140℃; for 72h; Sealed tube;	65%

cadmium(II) nitrate tetrhydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + 9,10-di(1-H-imidazol-1-yl)-anthracene → [Cd(9,10-di(1H-imidazol-1-yl)anthracene)(1,2-chdc)]n

Conditions	Yield
In water; N,N-dimethyl-formamide at 120℃; for 72h; Sealed tube;	63%

uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + Methyltriphenylphosphonium bromide (1779-49-3) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → [PPh3Me][H2NMe2]3[(UO2)4(R-t-1,2-chdc)6]·H2O

Conditions	Yield
In water at 140℃; for 168h; Autoclave; High pressure;	57%

1,2-bis(4'-pyridyl)ethane (4916-57-8) + nickel(II) chloride hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → C8H10O4(2-)*5H2O*Ni(2+)*C12H12N2

Conditions	Yield
With sodium hydroxide In water at 110℃; for 48h; Sealed tube;	52%

4,4'-bipyridine (553-26-4) + copper(II) perchlorate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → 3C10H8N2*3Cu(2+)*2C8H11O4(1-)*2C8H10O4(2-)*4H2O

Conditions	Yield
In water at 110℃; for 72h; Sealed tube;	49%

cadmium(II) nitrate tetrhydrate + 1,4-bis(pyridin-4-ylmethyl)piperazine (357429-12-0) + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → [Cd2(trans-1,2-cyclohexanedicarboxylate)2(bis(4-pyridylmethyl)piperazine)]n

Conditions	Yield
With sodium hydroxide In water at 120℃; for 48h; High pressure;	43%

uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + tetraphenylphosphonium bromide (2751-90-8) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → [PPh4][UO2(trans-(R)-1,2-cyclohexanedicarboxylate)(HCOO)]*(H2O)

Conditions	Yield
In water at 140℃; Autoclave; High pressure;	38%

(1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + Betulinic acid (472-15-1) → 3β-O-[(1'R,2'R)-2'-carboxycyclohexanecarbonyl]betulinic acid (1221184-26-4)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	35%

(1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + zinc(II) acetate dihydrate (5970-45-6) → 3Zn(2+)*2C8H10O4(2-)*2HO(1-)

Conditions	Yield
With sodium hydroxide In ethanol; water at 110℃; for 72h;	32.3%

[2,2]bipyridinyl (366-18-7) + uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → O2U(2+)*C8H10O4(2-)*C10H8N2

Conditions	Yield
In water; acetonitrile at 140℃; Autoclave; High pressure;	27%

18-crown-6 ether (17455-13-9) + uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + water (7732-18-5) + potassium nitrate → [(uranyl)10(potassium)5((1R,2R)-trans-1,2-cyclohexanedicarboxylate)4(oxalate)10(18-crown-6)5(OH)(H2O)3] tetrahydrate

Conditions	Yield
at 140℃; for 730.5h; High pressure;	27%

rubidium nitrate (13126-12-0) + uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → [H2NMe2][(UO2)4Rb3(R-trans-1,2-cyclohexanedicarboxylate)6(H2O)1.75]*DMF

Conditions	Yield
In water at 150℃; High pressure;	24%

sodium nitrate (7631-99-4) + uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → 2O2U(2+)*3C8H10O4(2-)*2Na(1+)*2H2O

Conditions	Yield
With 18-crown-6 ether In water; acetonitrile at 140℃; Autoclave; High pressure;	21%

hexadecylamine (143-27-1) + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → C40H78N2O2

Conditions	Yield
Stage #1: (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane for 0.25h; Inert atmosphere; Stage #2: hexadecylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 4h; Inert atmosphere;	11%

lead(II) nitrate + uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → 2O2U(2+)*3C8H10O4(2-)*4H2O*Pb(2+)

Conditions	Yield
In water; acetonitrile at 140℃; Autoclave; High pressure;	11%

caesium nitrate + uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → [(UO2)4Cs4(R-trans-1,2-cyclohexanedicarboxylate)6(H2O)4]·3H2O

Conditions	Yield
In methanol; water at 150℃; High pressure;	10%

[2,2]bipyridinyl (366-18-7) + copper nitrate hemi(pentahydrate) + uranyl nirate hexahydrate + (1R,2R)-(-)-trans-cyclohexane-1,2-dicarboxylic acid (46022-05-3) → O2U(2+)*2C8H10O4(2-)*C10H8N2*Cu(2+)*3H2O

Conditions	Yield
In water; acetonitrile at 140℃; Autoclave; High pressure;	9%

Upstream product

• 1687-29-2 dimethyl cis-1,2-cyclohexanedicarboxylate 
• 2305-32-0 trans-1,2-cyclohexanedicarboxylic acid 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 
• 88-98-2 cyclohex-4-ene-1,2-dicarboxylic acid 
• 88-98-2 trans-cyclohex-4-ene-1,2-dicarboxylic acid 
• 1292320-69-4 (1R,2R)-2-(nitromethyl)cyclohexane-1-carboxylic acid 

Downstream Products

• 85-42-7 trans-1,2-cyclohexanedicarboxylic anhydride 
• 158414-45-0 (R,R)-trans-2-aminocyclohexanecarboxylic acid hydrochloride 
• 186204-35-3 (1R,2R)-(-)-trans-cyclohexane-1,2-diylbis(methylene)dimethanesulfonate 
• 140459-96-7 (1R,2R)-1,2-cyclohexanedicarboxylic acid dimethyl ester 
• 41902-36-7 1,2-dimethyl cyclohex-2-ene-1,2-dicarboxylate 
• 4336-19-0 1,2-dimethyl cyclohex-1-ene-1,2-dicarboxylate 
• 194861-74-0 lurasidone 
• 367514-88-3 (3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(l1,2-benzisothiazol-3-yl)piperazin-1-yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione hydrochloride 
• 3205-34-3 (1S,2S)-(–)-1,2-di(hydroxymethyl)cyclohexane 
• 488703-60-2 (1S,2S)-2-((tert-butoxycarbonyl)amino)cyclohexane-1-carboxylic acid 
• 568588-47-6 (1S,2S)-2-((S)-2-Hydroxy-1-phenyl-ethylcarbamoyl)-cyclohexanecarboxylic acid methyl ester 
• 568588-48-7 (1S,2S)-Cyclohexane-1,2-dicarboxylic acid bis-[((S)-2-hydroxy-1-phenyl-ethyl)-amide] 
• 1374237-02-1 C₂₀H₂₀I₂N₂O₂ 
• 1263273-14-8 (1S,2S)-2-((3,5-dichlorophenyl)carbamoyl)cyclohexanecarboxylic acid 

Relevant articles and documents

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A PROCESS FOR PREPARATION OF TRANS (LR,2R)-CYCLO HEXANE 1, 2-DICARBOXYLIC ACID

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The present invention provides a process for the preparation of an antipsychotic agent useful for the treatment of schizophrenia.

Rational tuning chelate size of bis-oxazoline ligands to improve enantioselectivity in the asymmetric aziridination of chalcones

Chalcones were asymmetrically aziridinated with [N-(p-toluenesulfonyl) imino]phenyliodinane (PhI=NTs) as a nitrene source under catalysis of CuOTf and a series of cyclohexane-linked bis-oxazolines (cHBOXes), which are chelate size rationally tuned bis-oxazolines. The results indicate that highly enantioselective aziridination of chalcones with up to >99% ee have been achieved under catalysis of (S,S)-1,2-bis[(S)-(4-phenyl)oxazolin-2-yl] cyclohexane, which is the most-matched stereoisomer among cyclohexane-linked bis-oxazolines. It was also found that the enantioselectivity is not substituent-dependent with respect to chalcones in the present case, unlike with 1,8-anthracene-linked bis-oxazolines (AnBOXes).

Enantiomerically pure β-amino acids: A convenient access to both enantiomers of trans-2-aminocyclohexanecarboxylic acid

Enantiomerically pure trans-2-aminocyclohexanecarboxylic acid is an important building block for helical β-peptides. We report here that this amino acid can be obtained from trans-cyclohexane-1,2-dicarboxylic acid in good yield by a simple one-pot procedure comprising cyclization to the anhydride, amide formation with ammonia, and a subsequent Hofmann-type degradation with phenyliodine(III) bis(trifluoroacetate) (PIFA) as the oxidant. The N-Fmoc- and N-BOC-protected derivatives were obtained by treatment of the amino acid with Fmoc-OSu and BOC2O, respectively. The N-BOC derivative could be prepared in even better overall yield by a one-pot procedure leading directly from trans-cyclohexane-1,2-dicarboxylic acid to the N-BOC-protected amino acid. Both enantiomers of the starting trans-1,2-cyclohexanedicarboxylic acid can be obtained easily and in large quantities by separating commercially available racemic trans-1,2-cyclohexanedicarboxylic acid using either (R)- or (S)-1-phenethylamine. X-ray crystallography of the diastereomerically pure salt obtained from (R)-1-phenethylamine revealed that the configuration of the diacid component is (1R,2R), and not (1S,2S) as reported in the literature. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.