Cesium carbonate → Ethyl 2-(4-(benzyloxy)-2-formylphenoxy)-2-methylpropanoate

HRID 2229012Notes

Reaction equation

HRID 2229012 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([OH:17])=[C:13]([CH:16]=1)[CH:14]=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:19]([CH3:26])([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:23]([O:22][C:20](=[O:21])[C:19]([O:17][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:16][C:13]=1[CH:14]=[O:15])([CH3:26])[CH3:25])[CH3:24]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 8783625-(Benzyloxy)-2-hydroxybenzaldehyde

Product 1

HCID 53421768Ethyl 2-(4-(benzyloxy)-2-formylphenoxy)-2-methylpropanoateYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Benzyloxy-2-hydroxy-benzaldehyde (Kappe, T.; Witoszynskyj, T. Arch. Pharm. (1975), 308 (5), 339-346) (2.28 g, 10.0 mmol), ethyl bromoisobutyrate (2.2 mL, 15 mmol), and cesium carbonate (3.26 g, 10.0 mmol) in dry DMF (25 mL) were heated at 80° C. for 18 h. The reaction mixture was cooled and partitioned between water (30 mL) and ether (75 mL). The organic layer was washed with brine (15 mL). The aqueous layers were back-extracted with ethyl acetate (30 mL), and the organic layer was washed with brine (20 mL). The combined organic layers were dried (Na2SO4) and concentrated to a brown oil. The crude product was purified by flash chromatography using hexanes:ethyl acetate (2.5:1) to give a pale yellow solid (3.04 g, 89%): mp 65° C.; 1H NMR (400 MHz, CDCl3) δ1.24 (t, 3H, J=7.1 Hz), 1.62 (s, 6H), 4.23 (q, 2H, J=7.1 Hz), 6.81 (d, 1H, J=8.8 Hz), 7.10 (dd, 1H, J=4.6, 9.0 Hz), 7.30-7.43 (m, 6H); MS (ES) m/e 343.1 [M+1].

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between water (30 mL) and ether (75 mL)
  3. washThe organic layer was washed with brine (15 mL)
  4. extractionThe aqueous layers were back-extracted with ethyl acetate (30 mL)
  5. washthe organic layer was washed with brine (20 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated to a brown oil
  8. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-94068c21996c4596b7c769c3210e07b0
Source dataset
uspto-grants-2002_07
Patent number
US06417212B1

Reaction notes

Loading…