Sodium hydride → tert-Butyl 2-(3-(3-(3,4-dimethoxyphenyl)propanoyl)phenoxy)acetate

HRID 426394Notes

Reaction equation

HRID 426394 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH2:13][CH2:14][C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=2)=[O:16])[CH:8]=[CH:9][C:10]=1[O:11][CH3:12].[C:24]([O:28][C:29](=[O:32])[CH2:30]Br)([CH3:27])([CH3:26])[CH3:25]>CN(C=O)C>[C:24]([O:28][C:29]([CH2:30][O:23][C:19]1[CH:18]=[C:17]([C:15](=[O:16])[CH2:14][CH2:13][C:7]2[CH:8]=[CH:9][C:10]([O:11][CH3:12])=[C:5]([O:4][CH3:3])[CH:6]=2)[CH:22]=[CH:21][CH:20]=1)=[O:32])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 27716663-(3,4-Dimethoxyphenyl)-1-(3-hydroxyphenyl)propan-1-one

Product 1

HCID 2771667tert-Butyl 2-(3-(3-(3,4-dimethoxyphenyl)propanoyl)phenoxy)acetateYield 82.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A 60% mineral oil suspension of NaH (279 mg, 6.98 mmol) in anhydrous DMF (10 mL) was cooled to 0° C. in an ice bath and solid 3-(3,4-Dimethoxyphenyl)-1-(3-hydroxyphenyl)propan-1-one (7) (2 g, 6.98 mmol) added in one portion. The resulting yellow solution was stirred for 5 min after which time tert-butylbromoacetate (1.18 mL, 7.33 mmol) was added. Stirring was continued at 0° C. for 15 min after which time the reaction mixture was warmed to room temperature and partitioned between diethyl ether (50 mL) and water (50 mL). The organic layer was washed with a saturated NaCl solution (2×50 mL), dried over MgSO4, filtered, evaporated, and flash chromatographed (silica gel, 30% EtOAc/hexanes) to afford 2.30 g (82%) of a clear colorless oil: IR (neat) 2980, 1750, 1685, 1590, 1515, 1260, 1155 cm−1; 1H NMR (CDCl3, 300 MHz) 7.59 (d, J=7.7 Hz, 1H), 7.49 (s, 1H), 7.39 (app t, J=8.0 Hz, 1H), 7.14 (dd, J=8.2, 2.6 Hz, 1H), 6.81-6.79 (m, 3H), 4.58 (s, 2H), 3.89 (s, 3H), 3.88 (s, 3H), 3.28 (t, J=7.3 Hz, 2H), 3.02 (t, J=7.8 Hz, 2H), 1.51 (s, 9H); 13C NMR (CDCl3, 75 MHz) 199.2, 168.0, 158.6, 149.3, 147.8, 138.7, 134.2, 130.1, 121.8, 120.6, 113.5, 112.2, 111.8, 108.1, 83.0, 66.1, 56.2, 41.1, 30.2, 28.4.

Workup

  1. additionwas added
  2. temperatureafter which time the reaction mixture was warmed to room temperature
  3. custompartitioned between diethyl ether (50 mL) and water (50 mL)
  4. washThe organic layer was washed with a saturated NaCl solution (2×50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customflash chromatographed (silica gel, 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-272982b9da5344ab8a589e818eec2093
Source dataset
uspto-grants-2012_01
Patent number
US08106191B2

Reaction notes

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