(1S,3R,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol

Base Information

• Chemical Name: (1S,3R,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
• CAS No.: 72696-49-2
• Molecular Formula: C27H42 F2 O3
• Molecular Weight: 452.625
• Mol file: 72696-49-2.mol

Synonyms:24,24-difluoro-1,25-dihydroxyvitamin D3;24,24-difluorocalcitriol;F2-1,25(OH)2D3

Chemical Property of (1S,3R,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol

Chemical Property:

• Vapor Pressure: 6.37E-16mmHg at 25°C
• Boiling Point: 581.1°C at 760 mmHg
• Flash Point: 305.2°C
• PSA: 60.69000
• Density: 1.12g/cm³
• LogP: 5.94990
• XLogP3: 5.2
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 452.31020152
• Heavy Atom Count: 32
• Complexity: 769

Purity/Quality:

99%min ^*data from raw suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(CCC(C(C)(C)O)(F)F)C1CCC2C1(CCCC2=CC=C3CC(CC(C3=C)O)O)C
• Isomeric SMILES: C[C@H](CCC(C(C)(C)O)(F)F)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@@H](C[C@H](C3=C)O)O)C

Technology Process of (1S,3R,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol

There total 29 articles about (1S,3R,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-5,5-difluoro-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol 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: 95.0%

(R)-6-{(R)-4-[2-[(3S,5R)-3,5-Bis-(tert-butyl-dimethyl-silanyloxy)-2-methylene-cyclohex-(Z)-ylidene]-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-3,3-difluoro-2-methyl-heptan-2-ol (143884-28-0) → 24,24-difluoro-1α,25-dihydroxyvitamin D3 (72696-49-2,75227-86-0,94483-03-1)

Guidance literature:

With tetrabutyl ammonium fluoride; In tetrahydrofuran; Ambient temperature;

DOI:10.1248/cpb.40.1662

Reference yield: 95.0%

(5Z,7E)-1α,3β-bis(tert-butyldimethylsilyloxy)-24,24-difluoro-9,10-seco-5,7,10(19)-cholestatrien-25-ol → 24F2-1,25(OH)2-D3 (72696-49-2)

Guidance literature:

With tetrabutyl ammonium fluoride; In tetrahydrofuran; Ambient temperature;

DOI:10.1248/cpb.43.189

Reference yield:

1α,3β-dihydroxy-androst-5-en-17-one (20998-18-9) → 24F2-1,25(OH)2-D3 (72696-49-2)

Guidance literature:

Multi-step reaction with 16 steps

1: 89 percent / imidazole / dimethylformamide / 0.5 h / Ambient temperature

2: 98 percent / 2,6-lutidine / CH₂Cl₂ / 0.5 h / Ambient temperature

3: 100 percent / tert-BuOK / tetrahydrofuran / 4 h / Heating

4: 89 percent / BF₃*Et₂O / CH₂Cl₂ / 0.08 h / Ambient temperature

5: 95 percent / H₂ / 5percent Pt/C / ethanol / Ambient temperature

6: 1.) N-bromosuccinimide (NBS), NaHCO₃, 2.) n-Bu₄NBr / 1.) n-hexane, reflux, 1 h, 2.) THF, 0 deg C, 15 min

7: n-Bu₄NF / tetrahydrofuran / 3.5 h / 0 °C

8: 4-dimethylaminopyridine (DMAP) / CH₂Cl₂ / Ambient temperature

9: dimethylformamide / 1.5 h / 80 °C

10: diisobutylaluminum hydride (DIBAL-H) / hexane; diethyl ether / 0.25 h / 0 °C

11: 1.) Zn / 1.) THF, reflux, 2 min, 2.) THF, reflux, 15 min

12: 4-dimethylaminopyridine (DMAP) / CH₂Cl₂ / 1 h / Ambient temperature

13: azobisisobutyronitrile (AIBN), n-Bu₃SnH / toluene / 1 h / Heating

14: 98 percent / diethyl ether / 0.5 h / 0 °C

15: 98 percent / n-Bu₄NF / tetrahydrofuran / 1.) RT, overnight, 2.) 70 deg C, 1 h

16: 1.) ether, 0 deg C, irrad., 6 min, 2.) EtOH, reflux, 1 h

With 1H-imidazole; 2,6-dimethylpyridine; dmap; N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); boron trifluoride diethyl etherate; potassium tert-butylate; tetrabutyl ammonium fluoride; tetrabutylammomium bromide; hydrogen; tri-n-butyl-tin hydride; diisobutylaluminium hydride; sodium hydrogencarbonate; zinc; platinum on activated charcoal; In tetrahydrofuran; diethyl ether; ethanol; hexane; dichloromethane; N,N-dimethyl-formamide; toluene;

DOI:10.1248/cpb.40.1120

upstream raw materials:

24,24-difluorocholesta-5,7-dien-1α,3β,25-triol

1α,3β-dihydroxy-androst-5-en-17-one

1α,3β-bis<(tert-butyldimethylsilyl)oxy>-23,24-bisnorchol-5-en-22-ol

1α,3β-bis<(tert-butyldimethylsilyl)oxy>-23,24-bisnorchol-5,7-dien-22-ol

Refernces

• 1、 Konno,Ojima,Hayashi,Takayama. "An alternative and efficient synthesis of 24,24-difluoro-1α,25-dihydroxyvitamin D3". . p. 1120 - 1124. Retrieved 2007/10/02.
• 2、 -. "Immunosuppressive agents". . . Retrieved 2008/06/13.