Methyl iodide → O-benzyl-L-tyrosine

HRID 895367Notes

Reaction equation

HRID 895367 reaction equation
[H-].[Na+].C(OC([NH:10][C@H:11]([C:27]([OH:29])=[O:28])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:15][CH:14]=1)=O)(C)(C)C.CI.Cl.CCOCC>C1COCC1.CO>[C:21]1([CH2:20][O:19][C:16]2[CH:15]=[CH:14][C:13]([CH2:12][C@@H:11]([C:27]([OH:29])=[O:28])[NH2:10])=[CH:18][CH:17]=2)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 98763O-benzyl-N-((tert-butoxy)carbonyl)-L-tyrosineHCID 10953452Ether hydrochloride

Product 1

HCID 725701O-benzyl-L-tyrosine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH in THF (5 mL) cooled to 0° C. was added dropwise a solution of N-(tert-butyloxycarbonyl)-O-(phenylmethyl)-L-tyrosine, 1-[4-(2,3-dichlorophenyl)methyl]piperazine amide (N-Boc derivative of Example 159) (339 mg, 1.0 equiv). Methyl iodide (402 mg, 5 equiv) was then added to the reaction mixture via syringe. After the reaction was stirred at 0° C. for 30 minutes, it was warmed up to room temperature and stirred for 3 hours. An excess of methyl iodide and NaH was added to the reaction mixture (to achieve approximately 70% conversion) over 48 hours. After aqueous work up, the mixture was directly treated with HCl/Et2O in MeOH to afford the racemized titled product along with racemized O-(phenylmethyl)-L-tyrosine, 1-[4-(2,3-dichlorophenyl)methyl]piperazine amide (wherein the amine was not methylated). The mixture was then stirred with polymer bound benzaldehyde resin and filtered, thereby removing the racemized O-(phenylmethyl)-L-tyrosine, 1-[4-(2,3-dichlorophenyl)methyl]piperazine amide. The filtrate was concentrated in vacuo and the residue was further purified by preparative HPLC to afford the racemic titled compound, bis trifluoroacetic acid salt (100 mg) as a colorless oil (HPLC purity:100%): MS Calcd for [C28H31Cl2N3O2+H]+: 512. found: 512.

Workup

  1. temperatureit was warmed up to room temperature
  2. stirringstirred for 3 hours

Sources & evidence

ORD record
ord-e9b56476038342658a359005bde2ea20
Source dataset
uspto-grants-2005_07
Patent number
US06916812B2

Reaction notes

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