(4R,8S,9S,11S,12R,13S,19S)-12,19-Difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one

Base Information

• Chemical Name: (4R,8S,9S,11S,12R,13S,19S)-12,19-Difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one
• CAS No.: 67-73-2
• Molecular Formula: C24H30F2O6
• Molecular Weight: 452.495
• Hs Code.: 2937220000
• NSC Number: 757033
• Mol file: 67-73-2.mol

Synonyms:(4R,8S,9S,11S,12R,13S,19S)-12,19-Difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one;Spectrum_000819;Spectrum2_000964;Spectrum3_001747;Spectrum4_000554;Spectrum5_000710;BSPBio_003454;KBioGR_001247;KBioSS_001299;SPECTRUM1500302;SPBio_000967;SCHEMBL13046617;KBio2_001299;KBio2_003867;KBio2_006435;KBio3_002674;HMS2091F15;Pharmakon1600-01500302;CCG-40179;NSC757033;NSC-757033;NCGC00178053-01;SBI-0051384.P003;AB00051995_03;SR-05000001629;SR-05000001629-1;BRD-A77824596-001-01-6;BRD-A77824596-001-03-2

Chemical Property of (4R,8S,9S,11S,12R,13S,19S)-12,19-Difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one

Chemical Property:

• Appearance/Colour: Crystalline Solid
• Vapor Pressure: 8.57E-16mmHg at 25°C
• Melting Point: 267-269 °C(lit.)
• Refractive Index: 103 ° (C=1, MeOH)
• Boiling Point: 578.5 °C at 760 mmHg
• PKA: 12.78±0.70(Predicted)
• Flash Point: 303.7 °C
• PSA: 93.06000
• Density: 1.36 g/cm³
• LogP: 2.36680
• Storage Temp.: Refrigerator
• Solubility.: Practically insoluble in water, soluble in acetone and in ethanol
• Water Solubility.: Soluble in water (partly), DMSO, alcohol, chloroform and methanol.
• XLogP3: 2.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 2
• Exact Mass: 452.20104500
• Heavy Atom Count: 32
• Complexity: 960

Purity/Quality:

97.5%-103.0% ^*data from raw suppliers

Fluocinolone acetonide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi; Xn
• Hazard Codes: Xi,Xn
• Statements: 36/37/38-40-20/21/22
• Safety Statements: 26-36-22

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1(OC2CC3C4CC(C5=CC(=O)C=CC5(C4(C(CC3(C2(O1)C(=O)CO)C)O)F)C)F)C
• Isomeric SMILES: C[C@]12C[C@@H]([C@]3(C(C1C[C@@H]4[C@]2(OC(O4)(C)C)C(=O)CO)C[C@@H](C5=CC(=O)C=C[C@@]53C)F)F)O
• Uses: It is suitable in the treatment of eczema, neurodermatitis, skin pruritus, contact dermatitis, psoriasis, dermatitis and other diseases A synthetic glucocorticoid VEGF inhibitor; anti-inflammatory. Fluocinolone acetonide (Derma-Smoothe/FS, Flurosyn, Capex, Synalar) is a synthetic fluorinated corticosteroid. Fluocinolone acetonide is primarily used in dermatology to reduce skin inflammation and relieve itching. It acts as an inhibitor of tumor cells and it can regulate lipid metabolism by modulating gene expression. It can also inhibit the expression of VEGF (vascular endothelial growth factor) in the retinal pigment epithelial cell line due to its high glucocorticoid receptor affinity. Furthermore, it can inhibit TNF-α angiogenesis.
• Indications: Fluocinolone acetonide (Derma-Smoothe/FS, Flurosyn, Capex, Synalar) is a synthetic fluorinated corticosteroid.

Technology Process of (4R,8S,9S,11S,12R,13S,19S)-12,19-Difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one

There total 30 articles about (4R,8S,9S,11S,12R,13S,19S)-12,19-Difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.4%

fluocinonide (356-12-7) → fluocinolone Acetonide (67-73-2)

Guidance literature:

With sodium hydroxide; In dichloromethane; water; at 0 - 5 ℃; Inert atmosphere;

DOI:10.1246/cl.170923

Reference yield: 80.0%

11β,21-diacetoxy-6α,9α-difluoro-16α,17-[(1-methylethylidene)bis(oxy)]pregna-1,4-diene-3,20-dione → fluocinolone Acetonide (67-73-2)

Guidance literature:

With water; potassium carbonate; In methanol;

DOI:10.1002/jlcr.1575

Reference yield:

21-acetoxy-6α,9α-difluoro-11β-hydroxy-16α,17-[(1-methylethylidene)bis(oxy)]pregn-4-ene-3,20-dione (3932-49-8) → fluocinolone Acetonide (67-73-2)

Guidance literature:

Multi-step reaction with 3 steps

1: pyridine; dmap

2: benzeneseleninic anhydride / toluene / 7 h / Reflux

3: potassium carbonate / methanol; water

With pyridine; dmap; benzeneseleninic anhydride; potassium carbonate; In methanol; water; toluene;

DOI:10.1002/jlcr.1762

upstream raw materials:

fluocinonide

ethanol

(6α,11β,16α)-6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]pregna-1,4-diene-3,20-dione-21-(2'-phenoxypropionate)

21-acetoxy-6α,9α-difluoro-11β-hydroxy-16α,17-[(1-methylethylidene)bis(oxy)]pregn-4-ene-3,20-dione

Downstream raw materials:

fluocinonide

(6α,11β,16α)-6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]pregna-1,4-diene-3,20-dione-21-(2'-phenoxypropionate)

21-acetoxy-6α,9α-difluoro-11β-hydroxy-16α,17-[(1-methylethylidene)bis(oxy)]pregn-4-ene-3,20-dione

S-{[(4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-8-(2,4-difluorophenyl)-4b,12-difluoro-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6b-yl]carbonyl} dimethylthiocarbamate

Refernces

• 1、 -. "Synthesis method and application of 9-fluorosteroid compound". Paragraph 0143-0144; 0149-0150. . Retrieved 2021/01/15.
• 2、 -. "NOVEL PROCESS FOR PREPARATION OF CORTICOSTEROIDS". Page/Page column 18; 21. . Retrieved 2018/03/25.