172976-68-0

Synthetic route

(2-chlorophenyl)(phenyl)methanone (5162-03-8) + 4-Bromobenzoic acid (586-76-5) → (R,S) 2-chloro-4'-carboxy-triphenyl methanol (172976-68-0)

Conditions	Yield
With n-butyllithium	50%
With n-butyllithium 1.) THF, hexane, -78 deg C, 45 min, 2.) THF, hexane, from -78 deg C to RT, 1 h; Yield given. Multistep reaction;

2,3,4,5,6-pentafluorophenol (771-61-9) + (R,S) 2-chloro-4'-carboxy-triphenyl methanol (172976-68-0) → 2-chloro-4'-carboxytriphenylmethanol pentafluorophenyl ester (172976-56-6)

Conditions	Yield
With dicyclohexyl-carbodiimide In tetrahydrofuran for 3h;	80.3%

(R,S) 2-chloro-4'-carboxy-triphenyl methanol (172976-68-0) → 4-[Bromo-(2-chloro-phenyl)-phenyl-methyl]-benzoic acid pentafluorophenyl ester (172976-57-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80.3 percent / dicyclohexylcarbodiimide / tetrahydrofuran / 3 h 2: acetyl bromide / CH2Cl2 / 1.25 h / Ambient temperature View Scheme

(R,S) 2-chloro-4'-carboxy-triphenyl methanol (172976-68-0) → Nα-fluoren-9-ylmethoxycarbonylglycine-(2-chloro-4'-(carboxypentafluorophenoxy)triphenyl) methyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: 80.3 percent / dicyclohexylcarbodiimide / tetrahydrofuran / 3 h 2: acetyl bromide / CH2Cl2 / 1.25 h / Ambient temperature 3: diisopropylethylamine / CH2Cl2 / 1.25 h / Ambient temperature View Scheme

(R,S) 2-chloro-4'-carboxy-triphenyl methanol (172976-68-0) → Nα-fluoren-9-ylmethoxycarbonyl-β-alanine-(2-chloro-4'-(carboxypentafluorophenoxy)triphenyl) methyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: 80.3 percent / dicyclohexylcarbodiimide / tetrahydrofuran / 3 h 2: acetyl bromide / CH2Cl2 / 1.25 h / Ambient temperature 3: diisopropylethylamine / CH2Cl2 / 1.25 h / Ambient temperature View Scheme

(R,S) 2-chloro-4'-carboxy-triphenyl methanol (172976-68-0) → Nα-fluoren-9-ylmethoxycarbonylproline-(2-chloro-4'-(carboxypentafluorophenoxy)triphenyl) methyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: 80.3 percent / dicyclohexylcarbodiimide / tetrahydrofuran / 3 h 2: acetyl bromide / CH2Cl2 / 1.25 h / Ambient temperature 3: diisopropylethylamine / CH2Cl2 / 1.25 h / Ambient temperature View Scheme

aminomethyl-terminated Tentagel resin + (R,S) 2-chloro-4'-carboxy-triphenyl methanol (172976-68-0) → C21H17ClNO2Pol

Conditions	Yield
With diisopropyl-carbodiimide In N,N-dimethyl-formamide for 1h; solid phase reaction;

Upstream product

• 5162-03-8 (2-chlorophenyl)(phenyl)methanone 
• 586-76-5 4-Bromobenzoic acid 

Downstream Products

• 172976-56-6 2-chloro-4'-carboxytriphenylmethanol pentafluorophenyl ester 
• 172976-57-7 4-[Bromo-(2-chloro-phenyl)-phenyl-methyl]-benzoic acid pentafluorophenyl ester 

Relevant academic research and scientific papers

(R, S) 2-fluoro (chloro)-4′-carboxytriphenyl methanol. Novel acid labile trityl type handles for solid phase peptide synthesis

Novel trityl type handles have been prepared and applied to solid phase synthesis using 9 - fluorenylmethyloxycarbonyl (Fmoc) for Na - amino protection and acid labile protecting groups for side chain protection. The cleavage of the resultant ester can be carried out by using appropriate mild acidic cocktails 0.1 % (v/v) trifluoroacetic acid, and TFE : CH2Cl2 : CH3COOH 1: 8 : 1 (v/v).

Synthesis of the 3-repeat region of human tau-2 by the solid phase assembly of backbone amide-protected segments

The synthesis, purification, and use of N-(2-acetoxy-4-methoxybenzyl)(AcHmb) backbone amide protected segments in the preparation of Asp158-Leu251 from the 3-repeat region of human tau-2 has been investigated. Fmoc/tert-butyl based fully protected segments of 9-21 residues, containing appropriately placed AcHmb protection, were prepared on Polyhipe SU500 resin through a 2-chlorotrityl linker. Protected segments, cleaved with 0.75% trifluoroacetic acid in dichloromethane, were easily purified in 100s of milligram quantities by either silica gel chromatography or standard aqueous acetonitrile based reverse phase preparative HPLC. Purified protected segments, typically soluble at > 500 mg mL-1 in dimethylformamide, coupled efficiently and economically to a growing resin-bound assembly, to give the 94-mer human tau-2 with an overall purified yield of 2.50 μmol (16.7%).