Fludrocortisone Property

Melting point:

208-212°C

alpha 

D23 +139° (c = 0.55 in 95% ethanol)

Boiling point:

564.7±50.0 °C(Predicted)

Density 

1.1176 (estimate)

storage temp. 

Refrigerator

solubility 

DMSO (Slightly), Ethanol (Slightly, Heated), Methanol (Slightly, Sonicated)

form 

Solid

pka

12.11±0.70(Predicted)

color 

White to Off-White

Water Solubility 

111mg/L(25 ºC)

CAS DataBase Reference

127-31-1(CAS DataBase Reference)

EPA Substance Registry System

Hydrocortisone-9.alpha.-fluoro (127-31-1)

Safety

Hazard Codes 

Xn

Risk Statements 

63

Safety Statements 

22-26-36

Hazardous Substances Data

127-31-1(Hazardous Substances Data)

Toxicity

LD50 intraperitoneal in mouse: 170mg/kg

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H312Harmful in contact with skin

H332Harmful if inhaled

H361Suspected of damaging fertility or the unborn child

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P281Use personal protective equipment as required.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P308+P313IF exposed or concerned: Get medical advice/attention.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P322Specific measures (see …on this label).

P330Rinse mouth.

P363Wash contaminated clothing before reuse.

P405Store locked up.

P501Dispose of contents/container to..…

Fludrocortisone Chemical Properties,Usage,Production

Chemical Properties

White Solid

Originator

Alflorone Acetate,MSD,US,1954

Uses

A mineralocorticoid.

Definition

ChEBI: Fludrocortisone is a C21-steroid, a 3-oxo-Delta(4) steroid, a 20-oxo steroid, a 21-hydroxy steroid, a fluorinated steroid, a mineralocorticoid, a 17alpha-hydroxy steroid and an 11beta-hydroxy steroid. It has a role as an adrenergic agent and an anti-inflammatory drug. It derives from a hydride of a pregnane.

Manufacturing Process

Hydrocortisone acetate is first reacted with phosphorus oxychloride in pyridine to give the corresponding olefin. Then a sequence consisting of hypobromous acid addition, ring closure to the epoxide and ring opening with hydrogen fluoride gives fludrocortisone acetate. Preparation of a crystalline product is described then in US Patent 2,957,013.

brand name

Florinef (King).

Therapeutic Function

9-Fluoro-11β,17,21-trihydroxy-pregn-4-ene-3,20-dione acetate

Clinical Use

Fludrocortisone acetate is used orally for mineralocorticoid replacement therapy in patients with adrenocortical insufficiency, such as Addison's disease. This drug, introduced in 1954, helped to provide the impetus for the synthesis and biological evaluation of newer halogenated analogues.

Synthesis

Fludrocortisone, 9|á-fluoro-11|?,17|á,21-trihydroxypregn-4-en-3,20- dione (27.2.14), is synthesized from hydrocortisone acetate (27.1.17). In the first stage of synthesis, dehydration of the hydrocortisone molecules is accomplished using phosphorous chloride in pyridine, which forms a product with a double bond at C9¨CC11 27.2.11. The resulting double bond is synthesized into an epoxide by an initial transformation to a bromohydrine using N-bromoacetamide and subsequent dehydrobromination using sodium acetate, which forms 21-O-acetoxy-9d-11|?-epoxy-17|á-hydroxy-4-pregnen-3,20-dione (27.2.12). As described above, the epoxide ring is opened by hydrofluoric acid, which results in the formation of the 21-O-acetate of fludrocortisone 27.2.13. Hydrolysis of the acetyl group of this compound using potassium acetate gives fludrocortisone (27.2.14).