Sodium hydride → (2-Bromo-5-methoxy-3-methyl-benzyloxy)-acetic acid tert-butyl ester

HRID 2216113Notes

Reaction equation

HRID 2216113 reaction equation
[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[CH2:11][OH:12].[H-].[Na+].Br[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>CN(C=O)C.O>[C:20]([O:19][C:17](=[O:18])[CH2:16][O:12][CH2:11][C:3]1[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[C:7]([CH3:8])[C:2]=1[Br:1])([CH3:23])([CH3:22])[CH3:21]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 15304143(2-Bromo-5-methoxy-3-methylphenyl)methanol

Product 1

HCID 69586436(2-Bromo-5-methoxy-3-methyl-benzyloxy)-acetic acid tert-butyl esterYield 99.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of (2-bromo-5-methoxy-3-methyl-phenyl)-methanol ((Example 192: step c) 0.800 g, 3.46 mmol) in DMF (10 mL) was cooled to 0° C. and treated with NaH (0.100 g of 95% dispersion, 4.15 mmol) and allowed to warm to room temperature 30 min. The mixture was then treated with tert-butyl bromoacetate (0.614 mL, 4.15 mmol) and stirred at room temperature 1 h. The reaction was diluted with water and extracted with EtOAc (2×125 mL). The combined organic layers were washed well with water (3×300 mL), dried over MgSO4, and concentrated in vacuo to afford the product (2-bromo-5-methoxy-3-methyl-benzyloxy)-acetic acid tert-butyl ester (1.19 g, 98%) as a yellow oil. 1H NMR (CDCl3): δ 6.967 (d, 1H, J=2.8 Hz), 6.745 (d, 1H, J=3.2 Hz), 4.683 (s, 2H), 4.086 (s, 2H), 3.794 (s, 3H), 2.380 (s, 3H), 1.496 (s, 9H).

Workup

  1. extractionextracted with EtOAc (2×125 mL)
  2. washThe combined organic layers were washed well with water (3×300 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ad11af6c26b34159a59de9e1b3258051
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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