Chloroacetyl chloride → 8-Acetyl-6-(benzyloxy)-2H-1,4-benzoxazin-3(4H)-one

HRID 1967186Notes

Reaction equation

HRID 1967186 reaction equation
[OH:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][C:3]=1[C:19](=[O:21])[CH3:20].[CH3:22][CH:23]1CCC[O:24]1.[H][H].C(=O)([O-])[O-].[K+].[K+].ClCC(Cl)=O>[Pt](=O)=O.O>[C:19]([C:3]1[C:2]2[O:1][CH2:22][C:23](=[O:24])[NH:8][C:7]=2[CH:6]=[C:5]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:4]=1)(=[O:21])[CH3:20]

Participants

8

Reactant 5

HCID 6577Chloroacetyl chlorideHCID 73012-MethyltetrahydrofuranHCID 11430Potassium CarbonateHCID 210728231-(5-(Benzyloxy)-2-hydroxy-3-nitrophenyl)ethanoneHCID 178418361HCID 178418361, compound2×

Product 1

HCID 211001368-Acetyl-6-(benzyloxy)-2H-1,4-benzoxazin-3(4H)-one

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

15.00 kg (52.22 mol) 1-[2-hydroxy-3-nitro-5-(phenylmethoxy)-phenyl]-ethanone 4a, 0.165 kg platinum (IV) oxide and 45 l 2-methyltetrahydrofuran are hydrogenated at 3 bar hydrogen pressure and an internal temperature of 25° C. until no further hydrogen uptake is discernible. The catalyst is filtered off and washed with 20 l of 2-methyltetrahydrofuran. 23.09 kg (167.09 mol) potassium carbonate are placed in another reactor, and the reaction mixture from the first reactor is added. It is rinsed with 22 l of 2-methyltetrahydrofuran. Then within 30 minutes 9.44 kg (83.55 mol) chloroacetyl chloride are metered into the suspension. After 2.5 hours reaction time at 65° C., 101 l water are added. The aqueous phase is separated off at 55° C. Then 34 l 2-methyltetrahydrofuran are distilled off from the organic phase in vacuo. After heating to reflux temperature, 180 l methylcyclohexane are metered in within 30 minutes at reflux temperature. The suspension obtained is cooled to 20° C. and stirred for another 1 hour at this temperature to complete the crystallisation. Then the precipitate is removed by centrifuging, washed with 113 l methylcyclohexane and dried at 50° C.

Workup

  1. customan internal temperature of 25° C.
  2. filtrationThe catalyst is filtered off
  3. washwashed with 20 l of 2-methyltetrahydrofuran
  4. additionthe reaction mixture from the first reactor is added
  5. washIt is rinsed with 22 l of 2-methyltetrahydrofuran
  6. customAfter 2.5 hours reaction time at 65° C.
  7. customThe aqueous phase is separated off at 55° C
  8. distillationThen 34 l 2-methyltetrahydrofuran are distilled off from the organic phase in vacuo
  9. temperatureAfter heating
  10. temperatureto reflux temperature, 180 l methylcyclohexane
  11. customare metered in within 30 minutes
  12. temperatureat reflux temperature
  13. customThe suspension obtained
  14. customthe crystallisation
  15. customThen the precipitate is removed by centrifuging
  16. washwashed with 113 l methylcyclohexane
  17. customdried at 50° C.

Sources & evidence

ORD record
ord-2d573bfa90bf43dd835fa5c46f1f2565
Source dataset
uspto-grants-2013_04
Patent number
US08420809B2

Reaction notes

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