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

HRID 1181135Notes

Reaction equation

HRID 1181135 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.CCOC(C)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>[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

7

Reactant 3

HCID 10796Cesium carbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl ester2×HCID 8783625-(Benzyloxy)-2-hydroxybenzaldehyde

Product 1

HCID 53421768Ethyl 2-(4-(benzyloxy)-2-formylphenoxy)-2-methylpropanoateYield 83%

Reagents, catalysts & solvents 3

HCID 10796Cesium carbonateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Benzyloxy-2-hydroxy-benzaldehyde (Kappe, T.; Witoszynskyj, T. Arch. Pharm., 1975, 308 (5), 339-346) (169 g, 741 mmol), ethyl bromoisobutyrate (164 mL, 1.11 mol), and cesium carbonate (240 g, 741 mmol) in dry DMF (600 mL) were heated at 80° C. for 15 h. Additional cesium carbonate (5 g) and ethyl bromoisobutyrate (20 mL) were added, and the reaction mixture was heated for 6 h. The reaction mixture was cooled, diluted with EtOAc (4 L), and washed with water (3×2 L). The organic layer was dried (Na2SO4) and concentrated to a brown oil. The crude product was recrystallized from EtOAc (150 mL) with hexanes until turbid to give the title compound as a pale yellow solid (210 g, 83%): 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 was heated for 6 h
  2. temperatureThe reaction mixture was cooled
  3. washwashed with water (3×2 L)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated to a brown oil
  6. customThe crude product was recrystallized from EtOAc (150 mL) with hexanes until turbid

Sources & evidence

ORD record
ord-c750186f91c34849877f875776240e9d
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

Loading…