Hydrochloric Acid → Ethyl(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate

HRID 2114450Notes

Reaction equation

HRID 2114450 reaction equation
[Cl:1][C:2]1[C:3]([Cl:13])=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1.Br[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17].FC(F)(F)C(O)=O.Cl>CN(C=O)C.CC#N.O>[Cl:1][C:2]1[C:3]([Cl:13])=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[N:7]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]=2[CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 7748Ethyl bromoacetateHCID 574186546,7-dichloro-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 57488847Ethyl(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetateYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

A 1 L round-bottom flask was purged with argon and charged with sodium hydride (6.94 g of a 60% dispersion of NaH in mineral oil, 0.174 mol) and 60 mL of anhydrous DMF. This suspension was magnetically stirred and cooled to 0° C. in an ice-bath and then treated slowly with a suspension of 6,7-dichloro-2H-1,4-benzoxazin-3(4H)-one (22.2 g. 0.102 mol) in 140 mL of anhydrous DMF. The reaction mixture was maintained at 0° C. for one hour and then treated slowly with ethyl bromoacetate (29.4 mL, 0.265 mol) over a period of 5-10 minutes. This reaction mixture was maintained at 0° C. for thirty minutes, allowed to warm to room temperature, and then was maintained at room temperature for thirty minutes. HPLC (Eclipse XDB-C18, 4.6×250 mm, 5 micron, 1-99% CH3CN/H2O with 0.1% trifluoroacetic acid) showed that all of the starting material (Rt=6.2 min) was gone and that a new compound had formed (Rt=7.5 min). The reaction mixture was poured into 5.5 L of 5% aqueous HCl and the product precipitated immediately as a yellow solid. The suspension was stirred for 10 minutes and the solid was filtered off to give a yellow filter cake. The solid was rinsed with ice-cold ethanol (3×200 mL) and hexanes (3×200 mL) and then dried under high vacuum to give ethyl (6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate (26.0 g, 0.085 mol, 84%) as a white powder. MS (ES) m/e 304 [M+H]+.

Workup

  1. customA 1 L round-bottom flask was purged with argon
  2. additioncharged with sodium hydride (6.94 g of a 60% dispersion of NaH in mineral oil, 0.174 mol) and 60 mL of anhydrous DMF
  3. temperatureThe reaction mixture was maintained at 0° C. for one hour
  4. temperatureThis reaction mixture was maintained at 0° C. for thirty minutes
  5. temperatureto warm to room temperature
  6. temperaturewas maintained at room temperature for thirty minutes
  7. customhad formed (Rt=7.5 min)
  8. customthe product precipitated immediately as a yellow solid
  9. stirringThe suspension was stirred for 10 minutes
  10. filtrationthe solid was filtered off
  11. customto give a yellow filter cake
  12. washThe solid was rinsed with ice-cold ethanol (3×200 mL) and hexanes (3×200 mL)
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-f7354284ed2c4ce1b6d41554daeee4d7
Source dataset
uspto-grants-2008_10
Patent number
US07432258B2

Reaction notes

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