7635-54-3

Basic information

• Product Name: (+)-MENTHYL CHLOROFORMATE
• Synonyms: 2-isopropyl-5-Methylcyclohexyl carbonochloridate;(1S,2R,5S)-(+)-2-Isopropyl-5-methylcyclohex-1-yl chloroformate, (1S,2R,5S)-(+)-5-Methyl-2-(prop-2-yl)cyclohex-1-yl carbonochloridoate;(1S)-(+)-Menthyl chloroforMate optical purity ee: 97% (GLC);Carbonochloridic acid,5-methyl-2-(1-methylethyl)cyclohexyl ester, (1S,2R,5S)-;(+)-MENTHYL CHLOROFORMATE;(+)-CHLOROFORMYLOXY-P-MENTHANE;(+)-(1S)-MENTHYL CHLOROFORMATE;(1S)-(+)-MENTHYL CHLOROFORMATE
• CAS NO: 7635-54-3
• Molecular Formula: C₁₁H₁₉ClO₂
• Molecular Weight: 218.72
• Product Categories: chiral;Biochemistry;for Resolution of Alcohols & Thiols;for Resolution of Bases;Monocyclic Monoterpenes;Optical Resolution;Synthetic Organic Chemistry;Terpenes;Acid HalidesAsymmetric Synthesis;Chiral Resolving ReagentsDerivatization Reagents;Chiral Building Blocks;Chiral Resolution Reagents;Derivatization Reagents HPLC;Organic Building Blocks;UV-VIS
• Mol File: 7635-54-3.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 108-109 °C11 mm Hg(lit.)
• Flash Point: 158 °F
• Appearance: Colorless to light yellow liquid
• Density: 1.031 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0546mmHg at 25°C
• Refractive Index: n20/D 1.458(lit.)
• Storage Temp.: 2-8°C
• BRN: 2414685
• CAS DataBase Reference: (+)-MENTHYL CHLOROFORMATE(CAS DataBase Reference)
• NIST Chemistry Reference: (+)-MENTHYL CHLOROFORMATE(7635-54-3)
• EPA Substance Registry System: (+)-MENTHYL CHLOROFORMATE(7635-54-3)

Safety Data

• Hazard Codes: T,C
• Statements: 23-34-20/21/22
• Safety Statements: 26-36/37/39-45-25
• RIDADR: UN 3277 6.1/PG 2
• WGK Germany: 3
• F: 10-19-21
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 7635-54-3(Hazardous Substances Data)

Usage

Chemical Properties

Colorless to light yellow liqui

Uses

Chiral auxiliary in the asymmetric synthesis of quaternary carbon centers.

InChI:InChI=1/C11H19ClO2/c1-7(2)9-5-4-8(3)6-10(9)14-11(12)13/h7-10H,4-6H2,1-3H3/t8-,9+,10-/m0/s1

Synthetic route

bis(trichloromethyl) carbonate + (1S,2R,5S)-(+)-menthol (15356-60-2) → (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3)

Conditions	Yield
With pyridine In dichloromethane at -5 - 25℃; for 13h; Reagent/catalyst; Temperature; Solvent;	99%
Carbonylation;

phosgene (75-44-5) + (1S,2R,5S)-(+)-menthol (15356-60-2) → (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3)

Conditions	Yield
In tetrahydrofuran at 20℃; for 0.75h;	95%
In toluene

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + Anabasine (494-52-0) → (2'S)-[(1S,2R,5S)-menthoxycarbonyl]anabasine

Conditions	Yield
With triethylamine In tetrahydrofuran at 60℃; for 2h;	100%

1-((4R,5R)-4,5-dihydro-2-(6-((4R,5R)-4,5-dihydro-4,5-diphenyl-1H-imidazol-2-yl)pyridin-2-yl)-4,5-diphenylimidazol-1-yl)(mesityl)methanone + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → 2-(1-(2,4,6-trimethyl-benzoyl)-[4R,5R]-4,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-6-(1-((1S,2R,5S)-2-iso-propyl-5-methylcyclohexyl-3-oxycarbonyl)-[4R,5R]-4,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)pyridine

Conditions	Yield
With dmap In dichloromethane at 20℃; for 6h;	99%

aziridine-2-carboxylic acid ethyl ester (5950-36-7) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → 1-(-)-menthyloxycarbonyl-aziridine-2-carboxylic acid ethyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetone at 0 - 20℃;	99%

1,1'-binaphthalene-2,2'-dithiol (102555-71-5, 124414-36-4, 124414-37-5) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → Thiocarbonic acid O-((1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyl) ester S-[2'-((1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyloxycarbonylsulfanyl)-[1,1']binaphthalenyl-2-yl] ester + Thiocarbonic acid O-((1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyl) ester S-[2'-((1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyloxycarbonylsulfanyl)-[1,1']binaphthalenyl-2-yl] ester

Conditions	Yield
With triethylamine In benzene for 1h; Ambient temperature; Yields of byproduct given;	A 98% B n/a
With triethylamine In benzene for 1h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + 5-monoamino-25,26,27,28-tetrakis(propyloxy)-calix[4]arene (199923-84-7) → 5-menthyl carbamate-25,26,27,28-tetrapropoxycalix[4]arene

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃;	98%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + C12H17O4P → C23H35O6P

Conditions	Yield
With triethylamine In dichloromethane at 0 - 22℃; for 2.5h; Inert atmosphere;	97%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + 1,1'-bi-2-naphthol (602-09-5) → Carbonic acid (1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyl ester 2'-((1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyloxycarbonyloxy)-[1,1']binaphthalenyl-2-yl ester + Carbonic acid (1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyl ester 2'-((1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyloxycarbonyloxy)-[1,1']binaphthalenyl-2-yl ester

Conditions	Yield
With triethylamine In benzene for 1h; Ambient temperature; Yields of byproduct given;	A 95% B n/a
With triethylamine In benzene for 1h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + 1,2-(2,3-dihydro-1H-azirino)-<60>fullerene (156286-12-3) → C71H19NO2

Conditions	Yield
With pyridine In various solvent(s) at 70℃; for 1h;	95%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + BOC-Hyp-OtBu (170850-75-6) → (2S,4R)-di-tert-butyl 4-{[(1S,2R,5S)-2-isopropyl-5-methylcyclohexyloxy]carbonyloxy}pyrrolidine-1,2-dicarboxylate (865303-09-9)

Conditions	Yield
Stage #1: BOC-Hyp-OtBu With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: (+)-(1S,2R,5S)-menthylchloroformate In tetrahydrofuran at 20℃; for 22h;	95%

(3S)-3-(propan-2-yl)-3,4-dihydroquinoxalin-2(1H)-one (952060-29-6) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → C22H32N2O3 (1261061-28-2)

Conditions	Yield
With pyridine In dichloromethane at 20℃;	94%

4-(2-ethynyl-5-methoxyphenyl)-2-methylenebutan-1-ol (1046789-84-7) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → 4-(2-ethynyl-5-methoxyphenyl)-2-methylenebutyl (1R,2R,5S)-2-isopropyl-5-methylcyclohexyl carbonate (1046789-85-8)

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 2h;	93%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + t-butylphosphine-borane → C26H50BO4P

Conditions	Yield
With sodium hydride In tetrahydrofuran at -20 - 0℃;	92%

tert-butylphosphine-borane (162053-46-5) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → tert-butyl(dimenthyloxycarbonyl)phosphine borane

Conditions

Yield

With NaH In tetrahydrofuran (Ar); addn. slowly of (t-C4H9)PH2BH3 to mixt. of NaH (3 equiv.) and (+)menthyl chloroformate (2.2 equiv.) in THF at -20°C, warming to 0°C for 30 min, stirring for several hours; pouring of soln. onto ice/water containing HCl, sepn. of org. layer, extn. of aq. layer with ethyl acetate, washing of combined extracts with water and brine, drying (Na2SO4), concn. in vac., chromy. on SiO2 eluting with hexane/ethyl acetate, as oil;

92%

tryptamine (61-54-1) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl (2-(1H-Indol-3-yl)ethyl)carbamate (945910-39-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;	92%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + benzylamine (100-46-9) → Benzyl-carbamic acid (1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyl ester (683247-05-4)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h;	91%

2,6-bis-([4R,5R]-4,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-pyridine (863491-46-7) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → 2,6-bis-(1-((1S,2R,5S)-2-isopropyl-5-methylcyclohexyloxycarbonyl)-[4R,5R]-4,5-diphenyl-4,5-dihydro-1H-imidazol-2-yl)-pyridine

Conditions	Yield
With dmap In dichloromethane at 0 - 20℃;	90%
With dmap In dichloromethane at 20℃; for 1h;	90%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + 2-(4-methoxyphenyl)-4-methyl-5-oxo-4,5-dihydrooxazole (99553-79-4, 108509-76-8, 85380-77-4) → (S)-menthyl 2-(4-methoxyphenyl)-4-methyloxazol-5-yl carbonate (1017848-52-0)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃;	86%

L-leucine (61-90-5) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → N-[menthyloxycarbonyl]-L-leucine (1047650-51-0)

Conditions	Yield
Stage #1: L-leucine; (+)-(1S,2R,5S)-menthylchloroformate With sodium hydroxide In water at 0 - 20℃; Stage #2: With hydrogenchloride In water	85%

(S)-3-benzyl-3,4-dihydroquinoxalin-2(1H)-one (245554-93-2) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → C26H32N2O3 (1261061-27-1)

Conditions	Yield
With pyridine In dichloromethane at 20℃;	85%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + (+/-)-9H,9'H-[4,4']bicarbazole-3,3'-diol (475273-53-1, 475588-02-4, 475588-03-5) → Carbonic acid (1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyl ester 3'-((1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyloxycarbonyloxy)-9H,9'H-[4,4']bicarbazolyl-3-yl ester

Conditions	Yield
With triethylamine In acetonitrile	85%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + glycine (56-40-6) → N-(1S,3S,4R-menthyloxycarbonyl)glycine (1380401-10-4)

Conditions	Yield
With sodium hydrogencarbonate In 1,4-dioxane; water at 20℃; for 15h;	83%

1,1-dimethyl-1,3,4,9-tetrahydrospiro[carbazole-2,2'-[1,3]dioxolane] (958879-25-9) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl 1,1-dimethyl-3,4-dihydrospiro[carbazole-2,2'-[1,3]dioxolane]-9(1H)-carboxylate

Conditions	Yield
Stage #1: 1,1-dimethyl-1,3,4,9-tetrahydrospiro[carbazole-2,2'-[1,3]dioxolane] With sodium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: (+)-(1S,2R,5S)-menthylchloroformate In tetrahydrofuran at -78 - 20℃; for 2h; Further stages.;	80%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + aziridine-2-carboxylic acid isopropyl ester (5950-39-0) → 1-(-)-menthyloxycarbonyl-aziridine-2-carboxylic acid isopropyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetone at 0 - 20℃;	79%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + 4-hydroxymethylidene-2-phenyl-4,5-dihydrooxazol-5-one (1049019-27-3) → (Z)-(-)-menthyl 5-oxo-2-phenyloxazol-4-methylenecarbonate

Conditions	Yield
With triethylamine In dichloromethane at -5℃; for 3h;	78%

benzoxazole (273-53-0) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → 2-isocyanophenyl (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl carbonate (1158181-10-2)

Conditions	Yield
Stage #1: benzoxazole With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.5h; Stage #2: (+)-(1S,2R,5S)-menthylchloroformate In tetrahydrofuran; hexane at -78 - 20℃;	78%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + (+/-)-aziridine-2-carboxylic acid tert-butyl ester (82912-42-3) → 1-(-)-menthyloxycarbonyl-aziridine-2-carboxylic acid tert-butyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetone at 0 - 20℃;	78%

(+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) + methyl aziridine-2-carboxylate (5950-34-5, 118396-26-2, 151526-74-8, 151526-75-9) → 1-(-)-menthyloxycarbonyl-aziridine-2-carboxylic acid methyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetone at 0 - 20℃;	76%

N-benzyl-N-cyclopent-1-enyl-isonicotinamide (1429043-78-6) + (+)-(1S,2R,5S)-menthylchloroformate (7635-54-3) → C29H36N2O3 + (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl 3-benzyl-2-oxo-3,5,6,6a-tetrahydro-1’H,2H-spiro[cyclopenta[b]pyrrole-1,4’-pyridine]-1’-carboxylate

Conditions	Yield
With 2,6-dimethylpyridine In dichloromethane at 0 - 20℃; Inert atmosphere; Overall yield = 92 %;	A n/a B 75%

Upstream product

• 32315-10-9 bis(trichloromethyl) carbonate 
• 2216-51-5 (-)-menthol 
• 15356-60-2 (1S,2R,5S)-(+)-menthol 
• 75-44-5 phosgene 

Downstream Products

• 104461-75-8 1,4,4-Trimethyl-2-oxo-cyclopentanecarboxylic acid (1S,2R,5S)-2-isopropyl-5-methyl-cyclohexyl ester 
• 1202032-97-0 (R)-3-(tert-butyl)-3-oxido-2H-benzo[d][1,3]oxaphosphol-4-yl ((1S,2R,5S)-2-isopropyl-5-methylcyclohexyl) carbonate 

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