Hydrogen Bromide → 5-(2-bromoacetyl)-4-methylisobenzofuran-1(3H)-one

HRID 1848409Notes

Reaction equation

HRID 1848409 reaction equation
C([O:5][C:6]([C:8]1[C:9]([CH3:18])=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[O:12][CH2:11]2)=[CH2:7])CCC.C1C(=O)N([Br:26])C(=O)C1.Br>O.C1COCC1>[Br:26][CH2:5][C:6]([C:8]1[C:9]([CH3:18])=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[O:12][CH2:11]2)=[O:7]

Participants

6

Reactant 3

HCID 260Hydrogen BromideHCID 67184N-bromobutanimideHCID 675169525-(1-butoxy-vinyl)-4-methyl-3H-isobenzofuran-1-one

Product 1

HCID 772312635-(2-bromoacetyl)-4-methylisobenzofuran-1(3H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolvent4×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
19 °C

Procedure

To a 1 L 3-neck flask equipped with overhead stirrer was added crude 5-(1-butoxy-vinyl)-4-methyl-3H-isobenzofuran-1-one (55.8 g) and THF (315 mL). The solution was cooled to <5° C. after which water (79 mL) was added and the solution was maintained at <5° C. NBS (41.6 g) was then added portion-wise while maintaining Tmax=19° C. The solution was then warmed to RT for 30 minutes. HBr (48%, 0.241 mL) was added and the reaction was aged at RT for approximately 1 h after which 236 mL water was then added to the batch. A water bath is used to maintain temp at 20° C. Another 315 mL of water was added (solvent composition 1:2 THF:water) and the slurry was cooled to 15° C. The resulting solids were filtered and washed with cold 1:2 THF:water (15° C.): 150 mL displacement wash followed by 100 mL slurry wash. The solids were dried under vacuum at RT to provide 5-(2-bromo-acetyl)-4-methyl-3H-isobenzofuran-1-one. 1H NMR (400 MHz, DMSO-d6): δ 7.99 (d, J=7.8 Hz, 1H), 7.82 (d, J=7.8 Hz, 1H), 5.49 (s, 2H), 4.92 (s, 2H), 2.33 (s, 3H)

Workup

  1. customTo a 1 L 3-neck flask equipped with overhead stirrer
  2. additionwas added
  3. temperaturethe solution was maintained at <5° C
  4. temperatureThe solution was then warmed to RT for 30 minutes
  5. customA water bath is used
  6. temperatureto maintain temp at 20° C
  7. temperaturethe slurry was cooled to 15° C
  8. filtrationThe resulting solids were filtered
  9. washwashed with cold 1:2 THF
  10. washwater (15° C.): 150 mL displacement wash
  11. washwash
  12. customThe solids were dried under vacuum at RT

Sources & evidence

ORD record
ord-54fa9e28ef3d4af1bbef0d5fbab2fca8
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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