2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl morpholine

Base Information

• Chemical Name: 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl morpholine
• CAS No.: 171338-33-3
• Molecular Formula: C20H19F6NO2
• Molecular Weight: 419.36100
• DSSTox Substance ID: DTXSID50442931
• Wikidata: Q82260542
• Mol file: 171338-33-3.mol

Synonyms:171338-33-3;2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl morpholine;(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine;Morpholine, 2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenyl-,(2R,3S)-;SCHEMBL7019973;DTXSID50442931;2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)ethoxy)-3-(S)-phenyl morpholine

Chemical Property of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl morpholine

Chemical Property:

• Boiling Point: 388.7±42.0 °C(Predicted)
• PSA: 30.49000
• Density: 1.33±0.1 g/cm3(Predicted)
• LogP: 5.81780
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 4
• Exact Mass: 419.13199782
• Heavy Atom Count: 29
• Complexity: 498

Purity/Quality:

99% ^*data from raw suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC2C(NCCO2)C3=CC=CC=C3
• Isomeric SMILES: C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)O[C@@H]2[C@@H](NCCO2)C3=CC=CC=C3

Technology Process of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl morpholine

There total 5 articles about 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-phenyl morpholine 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: 75.0%

2-(R)-(1-(3,5-bis(tri-fluoromethyl)phenyl)ethenyloxy)-3-(S)-phenyl-4-benzyl morpholine (170729-73-4) → 2-(R)-(1-(S)-(3,5-bis(tri-fluoromethyl)phenyl)ethoxy)-3-(S)-phenyl morpholine (170729-74-5) + [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine (171338-33-3)

Guidance literature:

With hydrogen; palladium on activated charcoal; In ethyl acetate; isopropyl alcohol; for 48h;

DOI:10.1021/jm980299k

Reference yield: 53.0%

phenylmagnesium bromide (100-58-3) + (2R,2αR)-4-benzyl-2-[1-[3,5-bis(trifluoromethyl)phenyl]]ethoxy-morpholin-3-one (287930-75-0) → [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine (171338-33-3)

Guidance literature:

phenylmagnesium bromide; (2R,2αR)-4-benzyl-2-[1-[3,5-bis(trifluoromethyl)phenyl]]ethoxy-morpholin-3-one; In tetrahydrofuran; at 15 - 25 ℃; for 0.5h;

With 5%-palladium/activated carbon; hydrogen; toluene-4-sulfonic acid; In tetrahydrofuran; methanol; at 10 - 35 ℃; for 4h; under 258.581 Torr;

DOI:10.1021/op0501895

Reference yield:

3,5-bis(trifluoromethyl)phenyl carboxylic acid chloride (785-56-8) → [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine (171338-33-3)

Guidance literature:

Multi-step reaction with 3 steps

1: 1.) L-Selectride / 1.) THF, -78 deg C, 45 min, 2.) THF, -78 deg C, 30 min

2: 69 percent / tetrahydrofuran; toluene / 18 h / Heating

3: 75 percent / H₂ / 10percent Pd/C / ethyl acetate; propan-2-ol / 48 h

With hydrogen; L-Selectride; palladium on activated charcoal; In tetrahydrofuran; ethyl acetate; isopropyl alcohol; toluene;

DOI:10.1021/jm980299k

upstream raw materials:

2-(R)-(1-(3,5-bis(tri-fluoromethyl)phenyl)ethenyloxy)-3-(S)-phenyl-4-benzyl morpholine

3,5-bis(trifluoromethyl)phenyl carboxylic acid chloride

(S)-4-benzyl-3-phenylmorpholin-2-one

2-(R)-(3,5-bis(tri-fluoro-methyl)benzoyloxy)-3-(S)-phenyl-4-benzyl morpholine

Downstream raw materials:

aprepitant

Refernces

• 1、 Hale, Jeffrey J.,Mills, Sander G.,MacCoss, Malcolm,Finke, Paul E.,Cascieri, Margaret A.,Sadowski, Sharon,Ber, Elzbieta,Chicchi, Gary G.,Kurtz, Marc,Metzger, Joseph,Eiermann, George,Tsou, Nancy N.,Tattersall, F. David,Rupniak, Nadia M. J.,Williams, Angela R.,Rycroft, Wayne,Hargreaves, Richard,MacIntyre, D. Euan. "Structural optimization affording 2-(R)-(1-(R)-3,5- bis(trifluoromethyl)phenylethoxy)-3'-(S)-(4-fluoro)phenyl-4-(3-oxo-1,2,4- triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist". . p. 4607 - 4614. Retrieved 2007/10/03.