4-Fluorobenzyl bromide → 1-(4-fluoro-benzyl)-6-methyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione

HRID 1454222Notes

Reaction equation

HRID 1454222 reaction equation
[CH3:1][C:2]1[S:12][C:5]2[NH:6][C:7](=[O:11])[O:8][C:9](=[O:10])[C:4]=2[CH:3]=1.Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1>CN(C=O)C>[F:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:6]2[C:5]3[S:12][C:2]([CH3:1])=[CH:3][C:4]=3[C:9](=[O:10])[O:8][C:7]2=[O:11])=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 680214-Fluorobenzyl bromideHCID 138498796-Methyl-2H-thieno[2,3-d][1,3]oxazine-2,4(1H)-dione

Product 1

HCID 866032241-(4-fluoro-benzyl)-6-methyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dioneYield 41.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

step 3—Sodium hydride (1.5 g of a 60% dispersion in mineral oil, 37.5 mmol) was suspended in DMF (50 mL) in a 250 mL round-bottom flask equipped with a stir bar, and cooled to 0° C. and maintained under a nitrogen atmosphere. A solution of 61a (4.6 g, 25 mmol) dissolved in DMF (50 mL) was added dropwise through a septum. The flask was removed from the ice bath and the mixture was stirred at RT for 30 m. The reaction was cooled to 10° C. and 1-bromomethyl-4-fluoro-benzene (3.74 mL, 30 mmol) was added through the septum. The flask was removed from the ice bath and the mixture was stirred at RT for 2 h. The reaction was poured into ice and 1N HCl, extracted twice with EtOAc, dried (Na2SO4), filtered and concentrated. A solid was precipitated from the EtOAc by addition of Et2O and hexanes to afford 3.0 g (41%) of 1-(4-fluoro-benzyl)-6-methyl-1H-thieno[2,3-d][1,3]oxazine-2,4-dione (61b): ms 2[M+Na]=605.

Workup

  1. customequipped with a stir bar
  2. temperaturemaintained under a nitrogen atmosphere
  3. additionwas added dropwise through a septum
  4. customThe flask was removed from the ice bath
  5. temperatureThe reaction was cooled to 10° C.
  6. customThe flask was removed from the ice bath
  7. stirringthe mixture was stirred at RT for 2 h
  8. additionThe reaction was poured into ice and 1N HCl
  9. extractionextracted twice with EtOAc
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customA solid was precipitated from the EtOAc by addition of Et2O and hexanes

Sources & evidence

ORD record
ord-8d568fb0de7c4c66bb4834854f2c8bc8
Source dataset
uspto-grants-2009_01
Patent number
US07479489B2

Reaction notes

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