Chloromethyl ethyl ether → 18-Ethoxymethoxy-14-(4-methoxy-benzyl)-2,15-dioxo-3,14,16-triaza-tricyclo-[14.3.0.0*4,6*]nonadec-7-ene-4-carboxylic acid ethyl ester

HRID 570122Notes

Reaction equation

HRID 570122 reaction equation
[CH2:1]([O:3][C:4]([C:6]12[CH2:24][CH:23]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][N:15]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:14](=[O:34])[N:13]1[CH:9]([CH2:10][CH:11]([OH:35])[CH2:12]1)[C:8](=[O:36])[NH:7]2)=[O:5])[CH3:2].C(N(C(C)C)C(C)C)C.[CH2:46]([O:48][CH2:49]Cl)[CH3:47]>ClCCl>[CH2:1]([O:3][C:4]([C:6]12[CH2:24][CH:23]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][N:15]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:14](=[O:34])[N:13]1[CH:9]([CH2:10][CH:11]([O:35][CH2:49][O:48][CH2:46][CH3:47])[CH2:12]1)[C:8](=[O:36])[NH:7]2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 18523Chloromethyl ethyl ether2×HCID 81531Diisopropylethylamine2×HCID 6687090918-Hydroxy-14-(4-methoxy-benzyl)-2,15-dioxo-3,14,16-triaza-tricyclo-[14.3.0.0*4,6*]nonadec-7-ene-4-carboxylic acid ethyl ester

Product 1

HCID 6687066618-Ethoxymethoxy-14-(4-methoxy-benzyl)-2,15-dioxo-3,14,16-triaza-tricyclo-[14.3.0.0*4,6*]nonadec-7-ene-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the alcohol 27 (1.35 g, 2.70 mmol, 75% purity) and N-ethyl-diisopropylamine (1.42 ml, 8.1 mmol) in dichloromethane (15 ml) at 0° C. was added chloromethyl ethyl ether (0.5 ml, 5.4 mmol). After stirring at rt on the reaction mixture was cooled to 0° C. and more N-ethyldiisopropylamine (1 ml, 5.7 mmol) and chloromethyl ethyl ether (0.3 ml, 3.2 mmol) was added, then stirred additional 16 h at rt. The reaction mixture was then directly applied on a silicagel column and eluted using stepwise gradient elution (ethyl acetate in hexane 50-80%). Concentration of the appropriate fractions gave the title compound as a slight brown syrup which crystallized upon standing (0.8 g, 53%). LR-MS: Calcd for C30H44N3O7: 558. Found: 558 [M+H].

Workup

  1. temperaturewas cooled to 0° C.
  2. stirringstirred additional 16 h at rt
  3. washeluted
  4. washgradient elution (ethyl acetate in hexane 50-80%)

Sources & evidence

ORD record
ord-ffaf524fa9f9489cb23ca1ece1168716
Source dataset
uspto-grants-2015_05
Patent number
US09023808B2

Reaction notes

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