Dimethyl Sulfate → HCID 11809660, compound

HRID 849806Notes

Reaction equation

HRID 849806 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:19]([OH:21])=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([Cl:18])[CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22](OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.S(OC)(OC)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>O1CCOCC1.CC(C)=O.C(N(CC)CC)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:19]([OH:21])=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:22])=[C:13]([Cl:18])[CH:12]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 90495Di-tert-butyl dicarbonateHCID 26596932N-(tert-Butoxycarbonyl)-3-chloro-D-tyrosine

Product 1

HCID 11809660HCID 11809660, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Protected amino acid I was prepared from D-tyrosine in five steps. First, D-tyrosine was chlorinated with sulfuryl chloride in glacial acetic acid (R. Zeynek, Hoppe-Seyler's Z. f. Physiol. Chemie 1926, 144, 247-254). Next N-(tert-butoxycarbonyl)-3-(3-chloro-4-hydroxyphenyl)-D-a lanine was obtained in 94% yield by treating a suspension of the amino acid in 50% aqueous dioxane with di-tert-butyldicarbonate in the presence of triethylamine. The resulting product was dimethylated with dimethyl sulfate in the presence of potassium carbonate in refluxing acetone in 84% yield. The methyl ester was then saponified with sodium hydroxide in aqueous dioxane to yield N-(tert-butoxycarbonyl)-3-(3-chloro-4-methoxyphenyl)-D-a lanine in 86% yield. Exposure of the BOC-protected amino acid to trichloroethanol, pyridine and DCC in dichloromethane led to trichloroethyl ester I in 65% yield. Treatment of this material with trifluoroacetic acid led to a quantitative yield of the trifluoroacetate salt of I.

Workup

  1. additionby treating

Sources & evidence

ORD record
ord-e35fbe679b574905b8109bfc236a088d
Source dataset
uspto-grants-2000_01
Patent number
US06013626

Reaction notes

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