(1R)-7-(4-Chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-1-(4-hydroxyphenyl)-2-azaspiro[3.5]nonan-3-one

Base Information

• Chemical Name: (1R)-7-(4-Chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-1-(4-hydroxyphenyl)-2-azaspiro[3.5]nonan-3-one
• CAS No.: 194423-53-5
• Molecular Formula: C₂₆H₂₃ClFNO₃
• Molecular Weight: 451.925
• DSSTox Substance ID: DTXSID40433297
• Nikkaji Number: J902.823D
• Mol file: 194423-53-5.mol

Synonyms:SCH 58053

Chemical Property of (1R)-7-(4-Chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-1-(4-hydroxyphenyl)-2-azaspiro[3.5]nonan-3-one

Chemical Property:

• PSA: 60.77000
• LogP: 5.78580
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Ethanol (Slightly), Methanol (Slightly)
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 451.1350495
• Heavy Atom Count: 32
• Complexity: 673

Purity/Quality:

98% ^*data from raw suppliers

Sch 58053 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC(CCC12C(N(C2=O)C3=CC=C(C=C3)F)C4=CC=C(C=C4)O)(C5=CC=C(C=C5)Cl)O
• Isomeric SMILES: C1CC(CCC12[C@H](N(C2=O)C3=CC=C(C=C3)F)C4=CC=C(C=C4)O)(C5=CC=C(C=C5)Cl)O
• Uses: An analog of Ezetimibe (E975000). SCH 58053 is a potent, rapid, and selective inhibitor of lymphatic cholesterol transport in the intestine.

Technology Process of (1R)-7-(4-Chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-1-(4-hydroxyphenyl)-2-azaspiro[3.5]nonan-3-one

There total 8 articles about (1R)-7-(4-Chlorophenyl)-2-(4-fluorophenyl)-7-hydroxy-1-(4-hydroxyphenyl)-2-azaspiro[3.5]nonan-3-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:

(R)-3-(4-Benzyloxy-phenyl)-7-(4-chloro-phenyl)-2-(4-fluoro-phenyl)-7-hydroxy-2-aza-spiro[3.5]nonan-1-one (194367-71-0) → (R)-7-(4-Chloro-phenyl)-2-(4-fluoro-phenyl)-3-(4-hydroxy-phenyl)-2-aza-spiro[3.5]nonan-1-one + (R)-2-(4-Fluoro-phenyl)-7-hydroxy-3-(4-hydroxy-phenyl)-7-phenyl-2-aza-spiro[3.5]nonan-1-one + (R)-7-(4-Chloro-phenyl)-2-(4-fluoro-phenyl)-7-hydroxy-3-(4-hydroxy-phenyl)-2-aza-spiro[3.5]nonan-1-one (194423-53-5)

Guidance literature:

With hydrogen; palladium on activated charcoal; In ethanol; for 16h; under 2585.7 Torr; Yield given. Yields of byproduct given;

DOI:10.1021/jo9704366

Reference yield:

ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate (1489-97-0) → (R)-7-(4-Chloro-phenyl)-2-(4-fluoro-phenyl)-7-hydroxy-3-(4-hydroxy-phenyl)-2-aza-spiro[3.5]nonan-1-one (194423-53-5)

Guidance literature:

Multi-step reaction with 7 steps

1: 1.) LDA / 1) THF, -20 deg C, 1 h, 2) THF, -20 deg C, 30 min, -20 deg C --> rt, 1 h

2: N-(2-naphthalenesulfonyl)-D-valine, BH₃*THF / various solvent(s) / 3 h / -78 °C

3: n-Bu₄NF / tetrahydrofuran / 1 h / Ambient temperature

4: 1.) Me₃Al / 1) CH₂Cl₂, toluene, rt, 30 min; 2) CH₂Cl₂, toluene. 50-55 deg C, 2 d

5: BnNEt₃Cl, (EtO)2P(O)Cl, aq. NaOH / CH₂Cl₂ / 2 h / Ambient temperature

6: toluene; various solvent(s) / 1.5 h / 48 - 52 °C / further solvents and temperatures

7: ZnBr₂, H₂ / Pd/C / ethanol / 16 h / 2585.7 Torr

With sodium hydroxide; borane-THF; tetrabutyl ammonium fluoride; N-benzyl-N,N,N-triethylammonium chloride; hydrogen; trimethylaluminum; diethyl chlorophosphate; N-(2-naphthalenesulfonyl)-D-valine; zinc dibromide; lithium diisopropyl amide; palladium on activated charcoal; In tetrahydrofuran; ethanol; dichloromethane; toluene;

DOI:10.1021/jo9704366

Reference yield:

ethyl 4-oxocyclohexane-1-carboxylate (17159-79-4) → (R)-7-(4-Chloro-phenyl)-2-(4-fluoro-phenyl)-7-hydroxy-3-(4-hydroxy-phenyl)-2-aza-spiro[3.5]nonan-1-one (194423-53-5)

Guidance literature:

Multi-step reaction with 8 steps

1: 81 percent / 4-MeC₆H₄SO₃H / Heating

2: 1.) LDA / 1) THF, -20 deg C, 1 h, 2) THF, -20 deg C, 30 min, -20 deg C --> rt, 1 h

3: N-(2-naphthalenesulfonyl)-D-valine, BH₃*THF / various solvent(s) / 3 h / -78 °C

4: n-Bu₄NF / tetrahydrofuran / 1 h / Ambient temperature

5: 1.) Me₃Al / 1) CH₂Cl₂, toluene, rt, 30 min; 2) CH₂Cl₂, toluene. 50-55 deg C, 2 d

6: BnNEt₃Cl, (EtO)2P(O)Cl, aq. NaOH / CH₂Cl₂ / 2 h / Ambient temperature

7: toluene; various solvent(s) / 1.5 h / 48 - 52 °C / further solvents and temperatures

8: ZnBr₂, H₂ / Pd/C / ethanol / 16 h / 2585.7 Torr

With sodium hydroxide; borane-THF; tetrabutyl ammonium fluoride; N-benzyl-N,N,N-triethylammonium chloride; hydrogen; trimethylaluminum; diethyl chlorophosphate; toluene-4-sulfonic acid; N-(2-naphthalenesulfonyl)-D-valine; zinc dibromide; lithium diisopropyl amide; palladium on activated charcoal; In tetrahydrofuran; ethanol; dichloromethane; toluene;

DOI:10.1021/jo9704366

upstream raw materials:

(R)-3-(4-Benzyloxy-phenyl)-7-(4-chloro-phenyl)-2-(4-fluoro-phenyl)-7-hydroxy-2-aza-spiro[3.5]nonan-1-one

ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate

ethyl 4-oxocyclohexane-1-carboxylate

[(1,4-Dioxa-spiro[4.5]dec-8-ylidene)-ethoxy-methoxy]-trimethyl-silane

Refernces