Methyl iodide → (S)-N-(4-Azidobenzyl)-2-acetamido-3-methoxypropanamide

HRID 73132Notes

Reaction equation

HRID 73132 reaction equation
[N:1]([C:4]1[CH:20]=[CH:19][C:7]([CH2:8][NH:9][C:10](=[O:18])[C@@H:11]([NH:14][C:15](=[O:17])[CH3:16])[CH2:12][OH:13])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[CH3:21]I>>[N:1]([C:4]1[CH:20]=[CH:19][C:7]([CH2:8][NH:9][C:10](=[O:18])[C@@H:11]([NH:14][C:15](=[O:17])[CH3:16])[CH2:12][O:13][CH3:21])=[CH:6][CH:5]=1)=[N+:2]=[N-:3]

Participants

3

Reactant 2

HCID 6328Methyl iodideHCID 46179979HCID 46179979, compound

Product 1

HCID 45486401(S)-N-(4-Azidobenzyl)-2-acetamido-3-methoxypropanamideYield 81.3%

Procedure

Utilizing Method B, (S)—N-(4-Azidobenzyl)-2-acetamido-3-hydroxypropanamide (2.40 g, 8.66 mmol), Ag2O (10.04 g, 43.30 mmol), and MeI (5.40 mL, 86.60 mmol) gave crude (S)-5 after 4 d. The product was purified by column chromatography (SiO2; 1/9 MeOH/CHCl3) to obtain 2.05 g (81%) of (S)-5 as a white solid: mp 149-150° C.; [α]26D +15.4° (c 1.0, MeOH); Rf=0.5 (1/9 MeOH/CHCl3); IR (nujol mull) 3285, 2927, 2112, 1635, 1565, 1457 cm−1; 1H NMR (CDCl3) δ 2.03 (s, CH3C(O)), 3.38 (s, OCH3), 3.43 (dd, J=7.5, 9.0 Hz, CHH′OCH3), 3.81 (dd, J=4.2, 9.0 Hz, CHH′OCH3), 4.40 (½HH′q, J=6.0, 15.0 Hz, CHH′Ar), 4.46 (½HH′q, J=6.0, 15.0 Hz, CHH′Ar), 4.51-4.57 (m, CH), 6.43 (br d, J=6.3 Hz, NHCH), 6.78-6.83 (br m, NHCH2), 6.96-7.01 (m, 2 ArH), 7.23-7.27 (m, 2 ArH), addition of excess (R)-(−)-mandelic acid to a CDCl3 solution of (R)-5 gave only a single signal for the acetyl methyl protons and the ether methyl protons, addition of excess (R)-(−)-mandelic acid to a CDCl3 solution of (R)-5 and (S)-5 (1:2 ratio) gave two signals for the acetyl methyl protons (δ 1.995 (R) and 2.010 (S) (Δppm=0.015)), and the ether methyl protons (δ 3.302 (S) and 3.342 (R) (Δppm=0.040)); 13C NMR (CDCl3) δ 23.3 (CH3C(O)), 43.1 (CH2Ph), 52.7 (CH), 59.2 (CH2OCH3), 72.0 (CH2OCH3), 119.4, 129.1, 135.0, 139.4 (C6H5), 170.3, 170.6 (2C(O)); HRMS (ESI) 292.1405 [M+H+] (calcd. for C13H18N5O3 292.1410); Anal. (C13H17N5O3) Calcd.: C, 53.60%; H, 5.88%; N, 24.04%. Found: C, 53.76%; H, 5.97%; N, 24.22%.

Workup

  1. customgave crude (S)-5 after 4 d
  2. customThe product was purified by column chromatography (SiO2; 1/9 MeOH/CHCl3)

Sources & evidence

ORD record
ord-245c96f626174c0f9a943a08facbf07d
Source dataset
uspto-grants-2014_09
Patent number
US08829033B2

Reaction notes

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