Benzyl Bromide → Benzyl 2-hydroxy-2-methylpropanoate

HRID 1776646Notes

Reaction equation

HRID 1776646 reaction equation
[OH:1][C:2]([CH3:7])([CH3:6])[C:3]([OH:5])=[O:4].[H-].[Na+].Br[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1>[OH:1][C:2]([CH3:7])([CH3:6])[C:3]([O:5][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:4]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 116712-Hydroxyisobutyric acidHCID 24758Sodium hydride

Product 1

HCID 13908920Benzyl 2-hydroxy-2-methylpropanoateYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-hydroxy-2-methylpropanoic acid (500 mg, 4.80 mmol) in dry THF (10 ml), NaH (60% dispersion in mineral oil, 192 mg, 4.80 mmol) was added portionwise at 5° C. The resulting mixture was stirred 1 hour at RT. The solvent was removed, the residue was suspended in dry DMF (7 ml), and (bromomethyl)benzene (821 mg, 4.80 mmol) was added followed by a catalytic amount of KI. The reaction was heated under microwave irradiation at 100° C. for 3 hours. After cooling, the solvent was evaporated and the residue was partitioned between water and EtOAc; the organic phase was washed with brine, dried over sodium sulfate and evaporated to dryness. The residue was purified by flash chromatography on silica gel (EtOAc/petroleum ether=1/1) affording benzyl 2-hydroxy-2-methylpropanoate as a yellow liquid (773 mg, 3.98 mmol, 83% yield).

Workup

  1. customThe solvent was removed
  2. temperatureThe reaction was heated under microwave irradiation at 100° C. for 3 hours
  3. temperatureAfter cooling
  4. customthe solvent was evaporated
  5. customthe residue was partitioned between water and EtOAc
  6. washthe organic phase was washed with brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated to dryness
  9. customThe residue was purified by flash chromatography on silica gel (EtOAc/petroleum ether=1/1)

Sources & evidence

ORD record
ord-add1ab903269461e92bf494892233aea
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

Loading…