1-{[(9H-Fluoren-9-YL)methoxy]carbonyl}-4,4-difluoropyrrolidine-2-carboxylic acid

Base Information

• Chemical Name: 1-{[(9H-Fluoren-9-YL)methoxy]carbonyl}-4,4-difluoropyrrolidine-2-carboxylic acid
• CAS No.: 203866-21-1
• Molecular Formula: C₂₀H₁₇F₂NO₄
• Molecular Weight: 373.356
• Hs Code.: 2933990090
• European Community (EC) Number: 819-466-9
• Mol file: 203866-21-1.mol

Synonyms:1822492-40-9;1-{[(9H-FLUOREN-9-YL)METHOXY]CARBONYL}-4,4-DIFLUOROPYRROLIDINE-2-CARBOXYLIC ACID;MFCD01860709;SCHEMBL16095267;1-Fmoc-4,4-difluoro-DL-proline;(2S)-1-{[(9H-FLUOREN-9-YL)METHOXY]CARBONYL-4,4-DIFLUOROPYRROLIDINE-2-CARBOXYLIC ACID;(2S)-1-{[(9H-FLUOREN-9-YL)METHOXY]CARBONYL}-4,4-DIFLUOROPYRROLIDINE-2-CARBOXYLIC ACID;AKOS026739913;PB41740;SY219328;EN300-657602;(S)-1-Fmoc-4,4-difluoropyrrolidine-2-carboxylic Acid;1-[(9H-fluoren-9-ylmethoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acid;1-{[(9H-FLUOREN-9-YL)METHOXY]CARBONYL}-4,4-DIFLUOROPYRROLIDINE-2-CARBOXYLICACID

Chemical Property of 1-{[(9H-Fluoren-9-YL)methoxy]carbonyl}-4,4-difluoropyrrolidine-2-carboxylic acid

Chemical Property:

• Boiling Point: 550.2±50.0 °C(Predicted)
• PKA: 3.00±0.40(Predicted)
• PSA: 66.84000
• Density: 1.44±0.1 g/cm3(Predicted)
• LogP: 3.66760
• XLogP3: 3.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 4
• Exact Mass: 373.11256435
• Heavy Atom Count: 27
• Complexity: 577

Purity/Quality:

99%min ^*data from raw suppliers

Fmoc-L-Pro(4,4-F2)-OH ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1C(N(CC1(F)F)C(=O)OCC2C3=CC=CC=C3C4=CC=CC=C24)C(=O)O

Technology Process of 1-{[(9H-Fluoren-9-YL)methoxy]carbonyl}-4,4-difluoropyrrolidine-2-carboxylic acid

There total 7 articles about 1-{[(9H-Fluoren-9-YL)methoxy]carbonyl}-4,4-difluoropyrrolidine-2-carboxylic acid 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:

L-4-hydroxyproline methyl ester hydrochloride (40216-83-9) → (2S)-1-(9H-fluoren-9-ylmethoxycarbonyl)-4,4-difluoro-pyrrolidine-2-carboxylic acid (203866-21-1)

Guidance literature:

Multi-step reaction with 6 steps

1: 95 percent / Et₃N / CH₂Cl₂ / Ambient temperature

2: 81 percent / PDC, 3 Angstroem molecular sieves / CH₂Cl₂ / Ambient temperature

3: 89 percent / DAST / CH₂Cl₂ / -78 deg C to r.t.

4: 95 percent / LiOH / acetonitrile; H₂O / Ambient temperature

5: TFA / CH₂Cl₂

6: Et₃N / methanol

With lithium hydroxide; dipyridinium dichromate; 3 A molecular sieve; triethylamine; 4,4'-diaminostilbene-2,2'-disulfonic acid; trifluoroacetic acid; In methanol; dichloromethane; water; acetonitrile;

DOI:10.1016/S0040-4039(97)10793-6

Reference yield:

(fluorenylmethoxy)carbonyl chloride (28920-43-6) + sodium carbonate (497-19-8) + 1-(tert-butoxycarbonyl)-4,4-difluoro-L-proline (203866-15-3) + 1-tert-butyl 2-methyl (2S)-4,4-difluoropyrrolidine-1,2-dicarboxylate (203866-17-5) → (2S)-1-(9H-fluoren-9-ylmethoxycarbonyl)-4,4-difluoro-pyrrolidine-2-carboxylic acid (203866-21-1)

Guidance literature:

With lithium hydroxide; In tetrahydrofuran; 1,4-dioxane; dichloromethane; water; trifluoroacetic acid;

Reference yield:

1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate (74844-91-0) → (2S)-1-(9H-fluoren-9-ylmethoxycarbonyl)-4,4-difluoro-pyrrolidine-2-carboxylic acid (203866-21-1)

Guidance literature:

Multi-step reaction with 5 steps

1: 81 percent / PDC, 3 Angstroem molecular sieves / CH₂Cl₂ / Ambient temperature

2: 89 percent / DAST / CH₂Cl₂ / -78 deg C to r.t.

3: 95 percent / LiOH / acetonitrile; H₂O / Ambient temperature

4: TFA / CH₂Cl₂

5: Et₃N / methanol

With lithium hydroxide; dipyridinium dichromate; 3 A molecular sieve; triethylamine; 4,4'-diaminostilbene-2,2'-disulfonic acid; trifluoroacetic acid; In methanol; dichloromethane; water; acetonitrile;

DOI:10.1016/S0040-4039(97)10793-6

upstream raw materials:

N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide

(S)-4,4-difluoro-pyrrolidine-2-carboxylic acid

L-4-hydroxyproline methyl ester hydrochloride

1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate

Downstream raw materials:

(S)-1-((S)-1-(4-(benzyloxy)-3-fluorobenzoyl)-4,4-difluoropyrrolidine-2-carbonyl) pyrrolidine-2-carbonitrile

C₃₉H₆₄F₂N₁₂O₈

Refernces

• 1、 Demange, Luc,Menez, Andre,Dugave, Christophe. "Practical synthesis of Boc and Fmoc protected 4-fluoro and 4-difluoroprolines from trans-4-hydroxyproline". . p. 1169 - 1172. Retrieved 2007/10/03.