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Chemical Structure| 203866-14-2 Chemical Structure| 203866-14-2
Chemical Structure| 203866-14-2

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Boc-trans-4-F-Pro-OH is a protected trans-4-fluoro-L-proline derivative with the amino group protected by tert-butoxycarbonyl (Boc), suitable for peptide synthesis.

Synonyms: N-Boc-trans-4-fluoro-L-proline

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Product Details of Boc-trans-4-F-Pro-OH

CAS No. :203866-14-2
Formula : C10H16FNO4
M.W : 233.24
SMILES Code : O=C(N1[C@H](C(O)=O)C[C@@H](F)C1)OC(C)(C)C
Synonyms :
N-Boc-trans-4-fluoro-L-proline
MDL No. :MFCD06796085
InChI Key :YGWZXQOYEBWUTH-RQJHMYQMSA-N
Pubchem ID :12043048

Safety of Boc-trans-4-F-Pro-OH

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Application In Synthesis of Boc-trans-4-F-Pro-OH

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 203866-14-2 ]

[ 203866-14-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 89466-16-0 ]
  • [ 203866-14-2 ]
  • tert-butyl (2S,4R)-2-((6-bromo-3-methylpyridin-2-yl)carbamoyl)-4-fluoropyrrolidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% To a stirred solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylic acid (250 mg, 1.07 mmole) in 10 mL of CH2Cl2, was added 1-methyl imidazole (0.21 mL, 2.5 equiv.) at 0-50° C. under nitrogen atmosphere. The reaction mixture was stirred for 10 min at 0-50° C. and then added methane sulfonyl chloride (0.1 mL, 1.2 equiv) at the same temperature. It was stirred for 1 h at 0-5° C. Then <strong>[89466-16-0]6-bromo-3-methylpyridin-2-amine</strong> (200 mg, 1 equiv) was added, and stirred for 18h at room temperature. Water (10 mL) was added to the reaction mixture, layers were separated and aqueous layer was extracted with DCM (3×10 mL). The combined organic layer was washed with 1N HCl (10 mL), followed by Sat NaHCO3 (10 mL) and then with brine (10 mL). Combined organic layer was dried over Na2SO4, concentrated and 430 mg (quantitative yield) of titled compound was obtained.
Step 1: terf-Butyl (2S,4R)-2-((6-bromo-3-methylpyridin-2-yl)carbamoyI)-4- fluoropyrrolidine-l-carboxylate (209) [0696] To an ice cold solution of (2S,4R)-l -(feri-butoxycarbonyl)-4-fluoropyrrolidine-2- carbox lic acid (1 equiv) in DCM (10 vol) was added l-chloro-N,N,2-trimethyl-l-propenylamine ( 1 , 1 equiv) dropwise with stirring. Stirring was continued for 3 h at this temperature, and then 6- bromo-3-methylpyridin-2-amine (1.1 equiv) was added, followed by DIEA (3 equiv). The cooling bath was removed and the reaction mixture was stirred overnight at rt. The reaction mixture was then added to water and extracted with DCM. The organic layer was washed successively with an aqueous solution of NaHCCb, water and brine, then dried over Na2SO<i and concentrated under reduced pressure. The remaining residue was purified by column chromatography on silica gel (DCM EtOAc) to give compound 209.
  • 2
  • [ 1158786-59-4 ]
  • [ 203866-14-2 ]
  • tert-butyl (2S,4R)-2-((6-bromo-4-methoxypyridin-2-yl)carbamoyl)-4-fluoropyrrolidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% To an ice cold solution of (2S,4R)- 1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylic acid (250 mg, 1.1 mmole) in 6 mL of CH2Cl2, 1-chloro-N,N,2-trimethylprop-1-en-1-amine (0.15 mL, 1.1 equiv) was added drop-wise with stirring. The stirring was continued for 3 hours at the same temperature. Then <strong>[1158786-59-4]6-bromo-4-methoxypyridin-2-amine</strong> (239 mg, 1.0 equiv) was added, followed by 0.50 mL (3 equiv) Hunig's base. The cooling bath was removed and the reaction mixture was stirred at room temperature for overnight. The solvent was co-evaporated with 5 mL of MeOH, and the residue was purified by ISCO (eluted with ethyl acetate in hexane, gradient) to obtain 436 mg (97%) of tert-butyl-(2S,4R)-2-((6-bromo-4-methoxypyridine-2-yl)carbamoyl-4-fluoropyrrolidine-1-carboxylate as clear oil.
Step 1: ferf-Butyl (2S,4R)-2-((6-bromo-4-methoxypyridin-2-yl)carbamoyl)-4- fluoropyrrolidine-l-carboxylate (211) [0698] To an ice-cold solution of (2S,4R)~l-(/m-butoxycarbonyl)-4-fluoropyrro]idine-2- carboxylic acid (1 equiv) in DCM (10 vol) was added l-chloro-N,N,2-trimethyl-l-propenylamine ( 1.1 equiv) dropwise with stirring. The stirring was continued for 3 h at this temperature, and then <strong>[1158786-59-4]6-bromo-4-methoxypyridin-2-amine</strong> (1.1 equiv) was added, followed by DIEA (3 equiv). The cooling bath was removed and the reaction mixture was stirred overnight at rt. The reaction mixture was then added to water and extracted with DCM. The organic layer was washed successively with an aqueous solution of NaHCCb, water and brine, then dried over Na SC and concentrated under reduced pressure. The remaining residue was purified by column chromatography on silica gel (DCM/EtOAc) to give compound 211.
  • 3
  • [ 1005508-80-4 ]
  • [ 203866-14-2 ]
  • methyl 2-((2S,4R)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxamido)-6-chloroisonicotinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% To a stirred solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-fluoropyrrolidine-2-carboxylic acid (250 mg, 1.07 mmole) in 10 mL of CH2Cl2, was added 1-methyl imidazole (0.21 mL, 2.5 equiv.) at 0-5 C. under nitrogen atmosphere. The reaction mixture was stirred for 10 min at 0-5 C. and then added methane sulfonyl chloride (0.1 mL, 1.2 equiv) at the same temperature. It was stirred for 1 h at 0-50 C. Then <strong>[1005508-80-4]methyl 2-amino-6-chloroisonicotinate</strong> (201 mg, 1 equiv) was added, and stirred for 18 h at room temperature. Water (10 mL) was added to the reaction mixture, layers were separated and aqueous layer was extracted with DCM (3×10 mL). The combined organic layer was washed with 1N HCl (10 mL), followed by Sat NaHCO3 (10 mL) and then with brine (10 mL). Combined organic layer was dried over Na2SO4, concentrated and purified by ISCO (5% MeOH in DCM gradient) to obtain titled compound 130 mg (32% yield).
 

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