129101-36-6

Basic information

• Product Name: 2H-1-Benzopyran-2-carboxylic acid, 6-fluoro-3,4-dihydro-, (2S)-
• Synonyms: 2H-1-Benzopyran-2-carboxylic acid, 6-fluoro-3,4-dihydro-, (2S)-;(S)-6-Fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid;(2S)-6-Fluoro-2-[(2S)-oxiran-2-yl)-3,4-dihydro-2H – chromene (Isomer - A )
• CAS NO: 129101-36-6
• Molecular Formula: C₁₀H₉FO₃
• Molecular Weight: 196
• Mol File: 129101-36-6.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 358.0±42.0 °C(Predicted)
• Appearance: /
• Density: 1.364±0.06 g/cm3(Predicted)
• PKA: 3.05±0.20(Predicted)
• CAS DataBase Reference: 2H-1-Benzopyran-2-carboxylic acid, 6-fluoro-3,4-dihydro-, (2S)-(CAS DataBase Reference)
• NIST Chemistry Reference: 2H-1-Benzopyran-2-carboxylic acid, 6-fluoro-3,4-dihydro-, (2S)-(129101-36-6)
• EPA Substance Registry System: 2H-1-Benzopyran-2-carboxylic acid, 6-fluoro-3,4-dihydro-, (2S)-(129101-36-6)

Safety Data

• Hazardous Substances Data: 129101-36-6(Hazardous Substances Data)

Usage

General Description

2H-1-Benzopyran-2-carboxylic acid, 6-fluoro-3,4-dihydro-, (2S)- is a chemical compound that belongs to the class of benzopyrans. It is a derivative of 6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid, with the (2S)- stereochemistry. 2H-1-Benzopyran-2-carboxylic acid, 6-fluoro-3,4-dihydro-, (2S)- has potential applications in pharmaceutical research and drug development due to its structural features and potential biological activity. Its specific properties and potential uses may vary depending on the stereochemistry, which can influence its interactions and activities in biological systems. Further research into its pharmacological properties and potential therapeutic applications may lead to the development of new drugs or treatments.

Synthetic route

6-fluoro-4H-chromene-2-carboxylic acid → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
With C63H78IrNOP(2+)*C32H12BF24(1-); hydrogen; caesium carbonate In methanol at 60℃; under 4560.31 Torr; for 12h; Autoclave; enantioselective reaction;	99%

(S)-methyl 6-fluorochroman-2-carboxylate (1219915-01-1) → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Stage #1: (S)-methyl 6-fluorochroman-2-carboxylate With sodium hydroxide In tetrahydrofuran; methanol; water at 0 - 20℃; for 6h; Schlenk technique; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; water Schlenk technique;	95%

5-fluoro-2-hydroxybenzaldehyde (347-54-6) → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 6 h / 20 °C / Schlenk technique 2.1: potassium tert-butylate / tetrahydrofuran / 0 °C / Schlenk technique 3.1: hydrogenchloride / tetrahydrofuran; water / Schlenk technique; Reflux 4.1: sodium tetrahydroborate / methanol / 0 - 20 °C / Schlenk technique 5.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 6.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 7.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 8.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 9.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 10.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 10.2: Schlenk technique View Scheme
Multi-step reaction with 10 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 6 h / 20 °C / Schlenk technique 2.1: potassium tert-butylate / tetrahydrofuran / 0 °C / Schlenk technique 3.1: hydrogenchloride / tetrahydrofuran; water / Schlenk technique; Reflux 4.1: sodium tetrahydroborate / methanol / 0 - 20 °C / Schlenk technique 5.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 6.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 7.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 8.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 9.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 10.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 10.2: Schlenk technique View Scheme

2-[2-(benzyloxy)-5-fluorophenyl]ethan-1-ol → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 2.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 4.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 5.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 6.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 6.2: Schlenk technique View Scheme
Multi-step reaction with 6 steps 1.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 2.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 3.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 4.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 5.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 6.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 6.2: Schlenk technique View Scheme

C16H15FO2 → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: hydrogenchloride / tetrahydrofuran; water / Schlenk technique; Reflux 2.1: sodium tetrahydroborate / methanol / 0 - 20 °C / Schlenk technique 3.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 4.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 5.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 6.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 7.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 8.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 8.2: Schlenk technique View Scheme
Multi-step reaction with 8 steps 1.1: hydrogenchloride / tetrahydrofuran; water / Schlenk technique; Reflux 2.1: sodium tetrahydroborate / methanol / 0 - 20 °C / Schlenk technique 3.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 4.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 5.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 6.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 7.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 8.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 8.2: Schlenk technique View Scheme

C15H14FIO → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 3.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 4.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 5.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 5.2: Schlenk technique View Scheme
Multi-step reaction with 5 steps 1.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 3.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 4.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 5.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 5.2: Schlenk technique View Scheme

C13H15FO4 → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 2.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 3.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 3.2: Schlenk technique View Scheme
Multi-step reaction with 3 steps 1.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 2.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 3.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 3.2: Schlenk technique View Scheme

methyl 2-diazo-4-(5-fluoro-2-hydroxyphenyl)butanoate → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 2.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 2.2: Schlenk technique View Scheme
Multi-step reaction with 2 steps 1.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 2.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 2.2: Schlenk technique View Scheme

2-(benzyloxy)-5-fluorobenzaldehyde (312314-37-7) → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 9 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0 °C / Schlenk technique 2.1: hydrogenchloride / tetrahydrofuran; water / Schlenk technique; Reflux 3.1: sodium tetrahydroborate / methanol / 0 - 20 °C / Schlenk technique 4.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 5.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 6.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 7.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 8.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 9.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 9.2: Schlenk technique View Scheme
Multi-step reaction with 9 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0 °C / Schlenk technique 2.1: hydrogenchloride / tetrahydrofuran; water / Schlenk technique; Reflux 3.1: sodium tetrahydroborate / methanol / 0 - 20 °C / Schlenk technique 4.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 5.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 6.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 7.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 8.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 9.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 9.2: Schlenk technique View Scheme

2-(2-(benzyloxy)-5-fluorophenyl)acetaldehyde → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: sodium tetrahydroborate / methanol / 0 - 20 °C / Schlenk technique 2.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 3.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 4.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 5.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 6.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 7.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 7.2: Schlenk technique View Scheme
Multi-step reaction with 7 steps 1.1: sodium tetrahydroborate / methanol / 0 - 20 °C / Schlenk technique 2.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 20 °C / Schlenk technique 3.1: sodium hydride / mineral oil; tetrahydrofuran / Inert atmosphere; Schlenk technique; Reflux 4.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 5.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 6.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 7.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 7.2: Schlenk technique View Scheme

C20H21FO4 → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 2.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 3.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate; C35H30N2O2 / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 4.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 4.2: Schlenk technique View Scheme
Multi-step reaction with 4 steps 1.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 3040.2 Torr / Schlenk technique 2.1: triethylamine; Methanesulfonyl azide / acetonitrile / 20 °C / Schlenk technique 3.1: tetrakis(actonitrile)copper(I) hexafluorophosphate; C23H22N2O2; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate / dichloromethane / 0.08 h / 25 °C / Inert atmosphere; Schlenk technique; Glovebox 4.1: sodium hydroxide / methanol; tetrahydrofuran; water / 6 h / 0 - 20 °C / Schlenk technique 4.2: Schlenk technique View Scheme

6-fluoro-3,4-dihydro-2H-benzopyran-2-carboxylic acid ethyl ester → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: n-butyllithium; diisopropylamine / tetrahydrofuran; hexane / 1 h / -78 - -30 °C / Inert atmosphere 1.2: 3 h / -78 - 20 °C / Inert atmosphere 2.1: dihydrogen peroxide / tetrahydrofuran; hexane / 3 h / 0 °C / Inert atmosphere 3.1: sodium hydroxide / water; methanol / 5 h / 50 °C 4.1: caesium carbonate; hydrogen; C63H78IrNOP(2+)*C32H12BF24(1-) / methanol / 12 h / 60 °C / 4560.31 Torr / Autoclave View Scheme

C18H17FO3Se → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: dihydrogen peroxide / tetrahydrofuran; hexane / 3 h / 0 °C / Inert atmosphere 2: sodium hydroxide / water; methanol / 5 h / 50 °C 3: caesium carbonate; hydrogen; C63H78IrNOP(2+)*C32H12BF24(1-) / methanol / 12 h / 60 °C / 4560.31 Torr / Autoclave View Scheme

methyl 6-fluoro-4H-chromene-2-carboxylate → (S)-6-fluorochroman-2-carboxylic acid (129101-36-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water; methanol / 5 h / 50 °C 2: caesium carbonate; hydrogen; C63H78IrNOP(2+)*C32H12BF24(1-) / methanol / 12 h / 60 °C / 4560.31 Torr / Autoclave View Scheme

1,1'-oxybis(2-bromo-ethane) (5414-19-7) + (S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → C24H24F2O7

Conditions	Yield
With calcium oxide In dimethyl sulfoxide at 160℃; for 5h;	90%

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) + 1,2-bis(2-chloroethoxy)ethane (112-26-5) → C26H28F2O8

Conditions	Yield
With potassium hydroxide In N,N-dimethyl-formamide; toluene at 150℃; for 5h;	86%

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) + 3-oxa-1,5-dichloropentane (111-44-4) → C24H24F2O7

Conditions	Yield
With sodium hydrogencarbonate In toluene at 100℃; for 5.5h;	85%

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) + 1,4-dichlorobutane (110-56-5) → C24H24F2O6

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide at 120℃; for 5h;	82%

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) + N-[(2S)-4-amino-2-hydroxybicyclo[2.2.2]octan-1-yl]-2-(4-chloro-3-fluorophenoxy)acetamide → (2S)-N-{(3S)-4-[2-(4-chloro-3-fluorophenoxy)acetamido]-3-hydroxybicyclo[2.2.2]octan-1-yl}-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carboxamide

Conditions	Yield
With triethylamine; HATU In N,N-dimethyl-formamide	30%
With triethylamine; HATU In N,N-dimethyl-formamide	30%

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → (+)-(S)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carbonyl chloride

Conditions	Yield
With thionyl chloride In toluene at 65 - 70℃;
With thionyl chloride In toluene at 65 - 70℃;

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → 2-chloro-1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethanone (1219915-00-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: pivaloyl chloride; dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 20 - 50 °C / Large scale 2: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 3: sodium phosphate; sulfuryl dichloride / ethyl acetate / 10 °C / Large scale 4: acetic acid; hydrogenchloride / water / 7 h / 30 - 40 °C / Large scale View Scheme
Multi-step reaction with 5 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C 3: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 4: sodium phosphate; sulfuryl dichloride / ethyl acetate / 10 °C / Large scale 5: acetic acid; hydrogenchloride / water / 7 h / 30 - 40 °C / Large scale View Scheme
Multi-step reaction with 4 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 0.33 h / 20 - 25 °C / Large scale 1.2: 20 - 50 °C / Large scale 2.1: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 3.1: sulfuryl dichloride; sodium phosphate / ethyl acetate / 10 - 20 °C 4.1: hydrogenchloride / water; ethyl acetate; acetic acid / 3 h / 40 °C View Scheme

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → (R)-2-chloro-1-((S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol (1315508-93-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: pivaloyl chloride; dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 20 - 50 °C / Large scale 2: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 3: sodium phosphate; sulfuryl dichloride / ethyl acetate / 10 °C / Large scale 4: acetic acid; hydrogenchloride / water / 7 h / 30 - 40 °C / Large scale 5: isopropyl alcohol; NAD; (R)-selective alcohol dehydrogenase / aq. buffer / 24 h / 0 - 25 °C / pH 6.99 / Enzymatic reaction View Scheme
Multi-step reaction with 6 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C 3: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 4: sodium phosphate; sulfuryl dichloride / ethyl acetate / 10 °C / Large scale 5: acetic acid; hydrogenchloride / water / 7 h / 30 - 40 °C / Large scale 6: isopropyl alcohol; NAD; (R)-selective alcohol dehydrogenase / aq. buffer / 24 h / 0 - 25 °C / pH 6.99 / Enzymatic reaction View Scheme
Multi-step reaction with 5 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 0.33 h / 20 - 25 °C / Large scale 1.2: 20 - 50 °C / Large scale 2.1: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 3.1: sulfuryl dichloride; sodium phosphate / ethyl acetate / 10 - 20 °C 4.1: hydrogenchloride / water; ethyl acetate; acetic acid / 3 h / 40 °C 5.1: hydrogenchloride; NAD; triethanolamine; zinc(II) chloride / isopropyl alcohol; water; glycerol / 24 h / 0 - 25 °C / pH 6.99 / Enzymatic reaction View Scheme
Multi-step reaction with 6 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C 3: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 4: sulfuryl dichloride; sodium phosphate / ethyl acetate / 10 - 20 °C 5: hydrogenchloride / water; ethyl acetate; acetic acid / 3 h / 40 °C 6: hydrogenchloride; NAD; triethanolamine; zinc(II) chloride / isopropyl alcohol; water; glycerol / 24 h / 0 - 25 °C / pH 6.99 / Enzymatic reaction View Scheme

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → C16H15FO6

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C View Scheme
Multi-step reaction with 2 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C View Scheme

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → C16H19FO4

Conditions	Yield
Multi-step reaction with 2 steps 1: pivaloyl chloride; dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 20 - 50 °C / Large scale 2: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C 3: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale View Scheme
Multi-step reaction with 2 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 0.33 h / 20 - 25 °C / Large scale 1.2: 20 - 50 °C / Large scale 2.1: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C 3: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale View Scheme

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → C16H18ClFO4

Conditions	Yield
Multi-step reaction with 3 steps 1: pivaloyl chloride; dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 20 - 50 °C / Large scale 2: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 3: sodium phosphate; sulfuryl dichloride / ethyl acetate / 10 °C / Large scale View Scheme
Multi-step reaction with 4 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C 3: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 4: sodium phosphate; sulfuryl dichloride / ethyl acetate / 10 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1.1: dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 0.33 h / 20 - 25 °C / Large scale 1.2: 20 - 50 °C / Large scale 2.1: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 3.1: sulfuryl dichloride; sodium phosphate / ethyl acetate / 10 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: thionyl chloride / toluene / 65 - 70 °C 2: pyridine / dichloromethane / 6 h / 0 - 25 °C 3: trifluoroacetic acid / acetonitrile / 7 h / 50 - 55 °C / Large scale 4: sulfuryl dichloride; sodium phosphate / ethyl acetate / 10 - 20 °C View Scheme

cycl-isopropylidene malonate (2033-24-1) + (S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → C16H15FO6

Conditions	Yield
With dmap; pivaloyl chloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 20 - 50℃; Large scale;
Stage #1: cycl-isopropylidene malonate; (S)-6-fluorochroman-2-carboxylic acid With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 20 - 25℃; for 0.333333h; Large scale; Stage #2: With pivaloyl chloride In acetonitrile at 20 - 50℃; Large scale;

(S)-6-fluorochroman-2-carboxylic acid (129101-36-6) + 1,5-dichloropentane (628-76-2) → C25H26F2O6

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide; toluene at 80℃; for 6h;	1.7 g

1 ,6-dibromohexane (629-03-8) + (S)-6-fluorochroman-2-carboxylic acid (129101-36-6) → C26H28F2O6

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide at 140℃; for 4.5h;	1.7 g

Upstream product

• 99199-61-8 6-fluoro-3,4-dihydro-2H-benzopyran-2-carboxylic acid ethyl ester 
• 1219915-01-1 (S)-methyl 6-fluorochroman-2-carboxylate 
• 312314-37-7 2-(benzyloxy)-5-fluorobenzaldehyde 
• 347-54-6 5-fluoro-2-hydroxybenzaldehyde 

Downstream Products

• 155427-30-8 (+)-(S)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-carbonyl chloride 

Relevant articles and documents

Iridium-catalyzed enantioselective hydrogenation of unsaturated heterocyclic acids

Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF-=tetrakis[3,5- bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities. Copyright

Method of lowering the blood pressure

A method of potentiating the effects of blood pressure reducing agents in warm-blooded animals, said method comprising administering to said warm-blooded animals of an effective amount of a blood pressure reducing agent and a 2,2′-iminobisethanol derivative.