Tetrahydrofuran → (Z)-1-(2-(acetoxymethyl)-4-(tert-butoxycarbonylamino)-3-methylphenyl)-3-methoxy-3-oxoprop-1-en-2-yl benzoate

HRID 132438Notes

Reaction equation

HRID 132438 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11](I)=[CH:10][CH:9]=[C:8]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:7]=1[CH3:21])(=[O:3])[CH3:2].O1CCCC1.C(N(CC)CC)C.[C:34]([O:42][C:43]([C:45]([O:47][CH3:48])=[O:46])=[CH2:44])(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:34]([O:42]/[C:43](/[C:45]([O:47][CH3:48])=[O:46])=[CH:44]\[C:11]1[CH:10]=[CH:9][C:8]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:7]([CH3:21])[C:6]=1[CH2:5][O:4][C:1](=[O:3])[CH3:2])(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 641425Methyl 2-(benzoyloxy)-2-propenoateHCID 534147073-(Tert-butoxycarbonylamino)-6-iodo-2-methylbenzyl acetate

Product 1

HCID 59732069(Z)-1-(2-(acetoxymethyl)-4-(tert-butoxycarbonylamino)-3-methylphenyl)-3-methoxy-3-oxoprop-1-en-2-yl benzoateYield 95.5%

Reagents, catalysts & solvents 2

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalyst

Procedure

3-(tert-butoxycarbonylamino)-6-iodo-2-methylbenzyl acetate (18.0 g, 44.4 mmol) in tetrahydrofuran (180.00 ml, 2197 mmol) was added triethylamine (24.76 ml, 178 mmol) followed by tetrabutylammonium chloride, hydrate (13.15 g, 44.4 mmol) and 3-methoxy-3-oxoprop-1-en-2-yl benzoate (11.91 g, 57.7 mmol). After introducing nitrogen atmosphere, palladium(II)acetate (0.898 g, 4.0 mmol) was added. The reaction mixture was refluxed for 3 h. The crude product was cooled and most of the solvent was removed. The crude product was diluted with ether (300 mL) and solids were removed by filtration. The solvent was evaporated and the crude product was purified by flash chromatography using 30% EtOAc in hexane to 50% EtOAc in hexane. The product was crystallized from a mixture of EtOAc-hexane to give a white powder of (Z)-1-(2-(acetoxymethyl)-4-(tert-butoxycarbonylamino)-3-methylphenyl)-3-methoxy-3-oxoprop-1-en-2-yl benzoate (20.5 g, 42.4 mmol, 95% yield). 1H NMR (500 MHz, CDCl3): in δ 8.08-8.06 (m, 2H), 7.75-7.74 (m, 2H), 7.60-7.58 (m, 1H), 7.49-7.44 (m, 3H), 5.25 (s, 2H), 3.85 (m, 3H), 2.24 (s, 3H), 2.07 (s, 3H), 1.52 (s, 9H); MS (ESI) 506 (M+H); Rf=2.61.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was refluxed for 3 h
  3. customwas removed
  4. additionThe crude product was diluted with ether (300 mL) and solids
  5. customwere removed by filtration
  6. customThe solvent was evaporated
  7. customthe crude product was purified by flash chromatography
  8. customThe product was crystallized from a mixture of EtOAc-hexane

Sources & evidence

ORD record
ord-8ffd701e0c52419bbc48145d854ad8ed
Source dataset
uspto-grants-2008_06
Patent number
US07384931B2

Reaction notes

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