Treprostinil intermediate

Base Information

• Chemical Name: Treprostinil intermediate
• CAS No.: 101692-01-7
• Molecular Formula: C22H34O3
• Molecular Weight: 346.51
• Mol file: 101692-01-7.mol

Synonyms:Treprostinil intermediate;(alphaS,1R,2R,3aS,9aS)-2,3,3a,4,9,9a-Hexahydro-2-hydroxy-5-methoxy-alpha-pentyl-1H-benz[f]indene-1-propanol;(1R,2R,3aS,9aS)-1-(2-Hydroxyoctyl)-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol

Chemical Property of Treprostinil intermediate

Chemical Property:

• Melting Point: 71-72 °C
• Boiling Point: 509.0±50.0 °C(Predicted)
• PKA: 15.10±0.40(Predicted)
• PSA: 49.69000
• Density: 1.062±0.06 g/cm3(Predicted)
• LogP: 4.12840

Purity/Quality:

99% ^*data from raw suppliers

DescarboxyTreprostinil ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: Descarboxy Treprostinil is an impurity in the synthesis of Treprostinil (T719500), Synthetic analog of Prostacyclin (P839060). Antihypertensive. Treprostinil, marketed under the trade name Remodulin is a medication used to treat pulmonary arterial hypertension (PAH).

Technology Process of Treprostinil intermediate

There total 1 articles about Treprostinil intermediate 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:

2-allyl-3-methoxybenzaldehyde (94956-98-6) → (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol (101692-01-7)

Guidance literature:

Multi-step reaction with 8 steps

1: 92 percent / EtMgBr / tetrahydrofuran; diethyl ether / 0 - 20 °C

2: 75 percent / PCC / CH₂Cl₂ / 15 h / 0 - 20 °C

3: BH₃; Me₂S; (R)-methyloxazaborolidine / toluene; tetrahydrofuran / 1 h / -30 °C

4: 92 percent / imidazole; 4-(dimethylamino)pyridine / dimethylformamide; CH₂Cl₂ / 15 h / 20 °C

5: CH₂Cl₂ / 2 h / 20 °C

6: H₂; K₂CO₃ / Pd/C / ethanol / 20 °C / 4654.33 Torr

7: NaBH₄; aq. NaOH / ethanol / 6 h / -10 °C

8: 2162 g / TsOH / methanol / 15 h / 0 - 20 °C

With 1H-imidazole; dmap; sodium hydroxide; sodium tetrahydroborate; dimethylsulfide; (R)-methyloxazaborolidine; borane; ethylmagnesium bromide; hydrogen; potassium carbonate; toluene-4-sulfonic acid; pyridinium chlorochromate; palladium on activated charcoal; In tetrahydrofuran; methanol; diethyl ether; ethanol; dichloromethane; N,N-dimethyl-formamide; toluene; 3: Corey reduction / 5: Pauson-Khand cyclization;

DOI:10.1021/jo0347720

Reference yield: 95.0%

(1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol (101692-01-7) → (1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-1-((S)-3-hydroxyoctyl)-1H-cyclopenta[b]naphthalene-2,5-diol (101692-02-8)

Guidance literature:

With aluminum (III) chloride; 1-dodecylthiol; In dichloromethane; at 0 - 20 ℃; Inert atmosphere;

Reference yield:

(1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol (101692-01-7) → treprostinil (81846-19-7)

Guidance literature:

Multi-step reaction with 3 steps

1: 80 percent / Ph₂PH; n-BuLi / tetrahydrofuran; hexane / 20 h / Heating

2: 100 percent / K₂CO₃; tetrabutylammonium bromide / acetone / 8 h / Heating

3: 83 percent / aq. KOH / methanol / 3 h / Heating

With potassium hydroxide; n-butyllithium; tetrabutylammomium bromide; potassium carbonate; diphenylphosphane; In tetrahydrofuran; methanol; hexane; acetone;

DOI:10.1021/jo0347720

upstream raw materials:

2-allyl-3-methoxybenzaldehyde

Downstream raw materials:

(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-1-((S)-3-hydroxyoctyl)-1H-cyclopenta[b]naphthalene-2,5-diol

treprostinil

2-((1R,2R,3aS,9aS)-2-hydroxy-1-(S)-3-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalene-5-yloxylacetic acid ethyl ester

2-(((1R,2R,3aS,9aS)-2-hydroxy-1-((S)-3-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl)oxy)acetic acid diethanolamine salt

Refernces