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

HRID 860629Notes

Reaction equation

HRID 860629 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) are heated at 80° C. for 18 h. The reaction mixture is cooled and partitioned between water (30 mL) and ether (75 mL). The organic layer is washed with brine (15 mL). The aqueous layers are back-extracted with ethyl acetate (30 mL), and the organic layer is washed with brine (20 mL). The combined organic layers are dried (Na2SO4) and concentrated to a brown oil. The crude product is 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) δ 1.24 (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 is cooled
  2. custompartitioned between water (30 mL) and ether (75 mL)
  3. washThe organic layer is washed with brine (15 mL)
  4. extractionThe aqueous layers are back-extracted with ethyl acetate (30 mL)
  5. washthe organic layer is washed with brine (20 mL)
  6. dry with materialThe combined organic layers are dried (Na2SO4)
  7. concentrationconcentrated to a brown oil
  8. customThe crude product is purified by flash chromatography

Sources & evidence

ORD record
ord-52088af810364a58a51bc11fa43fbafc
Source dataset
uspto-grants-2006_12
Patent number
US07153878B2

Reaction notes

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