Cesium carbonate → 2-[4-Benzyloxy-2-(hydroxy-phenyl-methyl)-phenoxy]-2-methyl-propionic Acid Ethyl Ester

HRID 2229039Notes

Reaction equation

HRID 2229039 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([CH:16]([OH:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:31]([CH3:38])([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33]>CN(C=O)C>[CH2:35]([O:34][C:32](=[O:33])[C:31]([O:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10][C:11]=1[CH:16]([OH:23])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([CH3:38])[CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 222611734-Benzyloxy-2-(hydroxy-phenyl-methyl)-phenol

Product 1

HCID 693122172-[4-Benzyloxy-2-(hydroxy-phenyl-methyl)-phenoxy]-2-methyl-propionic Acid Ethyl EsterYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

4-Benzyloxy-2-(hydroxy-phenyl-methyl)-phenol (690 mg, 2.25 mmol) and Cs2CO3 (734 mg, 2.25 mmol) in DMF (7 mL) was treated with ethyl bromoisobutyrate (0.66 mL, 4.5 mmol) and heated at 55° C. for 16 h. Additional bromo ester (0.40 mL, 1.23 mmol) and Cs2CO3 (400 mg, 1.23 mmol) were added and the reaction mixture was heated for 40 h. The mixture was cooled and partitioned between ethyl acetate (30 mL) and H2O (10 mL). The organic layer was washed with brine (10 mL), dried (Na2SO4), and concentrated. The crude product was purified by flash chromatography using hexanes:ethyl acetate to give a pale yellow oil (615 mg, 65%): 1H NMR (400 MHz, CDCl3) δ1.21 (t, 3H, J=7.3 Hz), 1.39 (s, 3H), 1.43 (s, 3H), 4.19 (q, 2H, J=7.3 Hz), 4.97 (s 2H), 6.00 (s, 1H), 6.61 (d, 1H, J=8.8 Hz), 6.74 (dd, 2H, J=3.2, 9.0 Hz), 6.96 (d, 1H, J=2.9 Hz), 7.22-7.39 (m, 10).

Workup

  1. temperaturethe reaction mixture was heated for 40 h
  2. temperatureThe mixture was cooled
  3. custompartitioned between ethyl acetate (30 mL) and H2O (10 mL)
  4. washThe organic layer was washed with brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-debf565ebda64678b9bd859f912f43bc
Source dataset
uspto-grants-2002_07
Patent number
US06417212B1

Reaction notes

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