1,8-Diazabicyclo(5.4.0)undec-7-ene → 1-(2-Tert-butoxycarbonyl-4-methoxy-but-2e-enyl)-cyclopentane carboxylic acid

HRID 22912Notes

Reaction equation

HRID 22912 reaction equation
[C:1]([O:5][C:6]([CH:8]1[CH2:17][C:12]2([CH2:16][CH2:15][CH2:14][CH2:13]2)[C:11](=[O:18])[O:10][CH:9]1[CH2:19][O:20][CH3:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1>[C:1]([O:5][C:6](/[C:8](=[CH:9]/[CH2:19][O:20][CH3:21])/[CH2:17][C:12]1([C:11]([OH:18])=[O:10])[CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 697464568-Methoxymethyl-6-oxo-7-oxa-spiro[4.51decane-9-carboxylic acid tert-butyl ester

Product 1

HCID 225923821-(2-Tert-butoxycarbonyl-4-methoxy-but-2e-enyl)-cyclopentane carboxylic acidYield 29%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of the product from stage b) above (6.11 g, 20.49 mmol) in toluene (50 ml) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.7 ml, 24.58 mmol), and the resultant solution was then heated at reflux under nitrogen for 5 h. The solution was then cooled to room temperature and the solvent was removed under reduced pressure. To the resultant residue was then added deionised water (100 ml) and the mixture was then extracted with tert-butyl methyl ether (30 ml). The phases were then separated and the aqueous phase was acidified to pH 2 with hydrochloric acid (15 ml of a 2 M solution) and then extracted with tert-butyl methyl ether (2×30 ml). The combined organic extracts were then washed with water (30 ml) and then brine (30 ml) and dried over magnesium sulfate. The solvent was then removed under reduced pressure to give the crude title compound (6.29 g), which was then crystallised from heptane (15 ml) at 0° C. The resultant solid was collected by filtration was then washed with ice-cold heptane (2×5 ml) to give the title compound as a white solid (1.79 g, 6.0 mmol, 29%, E-isomer assigned on basis of chemical shifts); 1H NMR (400 MHz, CDCl3), δ: 1.47 (s, 9H), 1.45-1.70 (m, 6H), 2.05-2.10 (m, 2H), 2.74 (s, 2H), 3.36 (s, 3H), 4.09 (d, 2H), 6.75 (t, 1H); 13C NMR (100 MHz, CDCl3) δ: 23.9, 28.0, 34.1, 35.0, 55.0, 58.6, 69.2, 80.8, 132.7, 139.1, 167.1, 183.3.

Workup

  1. temperatureat reflux under nitrogen for 5 h
  2. customthe solvent was removed under reduced pressure
  3. additionTo the resultant residue was then added deionised water (100 ml)
  4. extractionthe mixture was then extracted with tert-butyl methyl ether (30 ml)
  5. customThe phases were then separated
  6. extractionthen extracted with tert-butyl methyl ether (2×30 ml)
  7. washThe combined organic extracts were then washed with water (30 ml)
  8. dry with materialbrine (30 ml) and dried over magnesium sulfate
  9. customThe solvent was then removed under reduced pressure
  10. customto give the crude title compound (6.29 g), which
  11. customwas then crystallised from heptane (15 ml) at 0° C
  12. filtrationThe resultant solid was collected by filtration
  13. washwas then washed with ice-cold heptane (2×5 ml)

Sources & evidence

ORD record
ord-4ae714f6ef6142139ce4e505758ada78
Source dataset
uspto-grants-2005_02
Patent number
US06849649B2

Reaction notes

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