1-{[4-Ethoxymethoxy-2-(hex-5-enyl-methyl-carbamoyl)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester → 17-Ethoxymethoxy-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]-octadec-7-ene-4-carboxylic acid ethyl ester

HRID 1445417Notes

Reaction equation

HRID 1445417 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][CH2:20][O:21][CH2:22][CH3:23])[CH2:16][CH:15]2[C:24](=[O:33])[N:25]([CH2:27][CH2:28][CH2:29][CH2:30][CH:31]=C)[CH3:26])=[O:13])[CH2:8][CH:7]1[CH:9]=C)=[O:5])[CH3:2]>ClC(Cl)C>[CH2:1]([O:3][C:4]([C:6]12[CH2:8][CH:7]1[CH:9]=[CH:31][CH2:30][CH2:29][CH2:28][CH2:27][N:25]([CH3:26])[C:24](=[O:33])[CH:15]1[CH:14]([CH2:18][CH:17]([O:19][CH2:20][O:21][CH2:22][CH3:23])[CH2:16]1)[C:12](=[O:13])[NH:11]2)=[O:5])[CH3:2]

Participants

3

Reactant 1

HCID 668711271-{[4-Ethoxymethoxy-2-(hex-5-enyl-methyl-carbamoyl)-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 6687123617-Ethoxymethoxy-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]-octadec-7-ene-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

A degassed solution of dialkene (114)(1.83 g, 3.93 mmol) in dichloroethane (1.8 L, stored over 4 Å molecular sieves before use) was added Howeyda-Grubbs 1st generation catalyst (0.165 g, 0.27 mmol), then shortly degassed and stirred at approximately 85° C. bath temperature overnight (monitored by LC-MS). The reaction mixture was then allowed to cool somewhat after which solid phase catalyst scavenger (1.3 g, MP-TMT, Argonaut Technologies) and stirred additional 1.5 h, then filtered and concentrated. Flash chromatography of the residue (YMC-GEL silica) using stepwise gradient elution (ethyl acetate in hexane, 50-100%) and concentration of the appropriate fractions gave the title compound as a brown syrup which crystallized upon standing (1.33 g, 77%, purity approx. 90%). This material was crystallized from 4:1 ethyl acetate (40 ml) giving a brown solid (0.79 g, 1.8 mmol) and chromatography of the mother liqure gave additional product (0.36 g, 0.81 mmol). LR-MS: Calcd for C23H37N2O6: 437. Found: 437 [M+H].

Workup

  1. customshortly degassed
  2. temperatureto cool somewhat after which solid phase catalyst scavenger (1.3 g, MP-TMT, Argonaut Technologies)
  3. stirringstirred additional 1.5 h
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washelution (ethyl acetate in hexane, 50-100%) and concentration of the appropriate fractions

Sources & evidence

ORD record
ord-c63aac21e605407c9cf3cf2df26c6f50
Source dataset
uspto-grants-2010_02
Patent number
US07666834B2

Reaction notes

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