Sodium Hydroxide → 5-Difluoromethyl-5-(2-fluoro-6-nitro-phenyl)-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

HRID 81610Notes

Reaction equation

HRID 81610 reaction equation
[N+:1]([O-:4])([O-])=[O:2].[K+].[F:6][CH:7]([F:22])[C:8]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:13][O:12][CH2:11][C:10]([NH2:14])=[N:9]1.CC(OC)(C)C.[OH-].[Na+]>S(=O)(=O)(O)O>[F:22][CH:7]([F:6])[C:8]1([C:15]2[C:20]([N+:1]([O-:4])=[O:2])=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:13][O:12][CH2:11][C:10]([NH2:14])=[N:9]1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 15413tert-Butyl methyl etherHCID 24434Potassium NitrateHCID 666659065-Difluoromethyl-5-(2-fluoro-phenyl)-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

Product 1

HCID 867165345-Difluoromethyl-5-(2-fluoro-6-nitro-phenyl)-5,6-dihydro-2H-[1,4]oxazin-3-ylamineYield 97.9%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent2×

Procedure

Potassium nitrate (60.3 g, 596 mmol) was added portionwise to 600 ml sulfuric acid (Temperature<20° C.). This solution was added dropwise to a solution of 5-difluoromethyl-5-(2-fluoro-phenyl)-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (112 g, 459 mmol) in 600 ml sulfuric acid, while keeping the reaction temperature<22° C. with an ice bath. After stirring for 1 h, the mixture was poured onto 10 Kg ice. TBME (6 L) was added and the pH was adjusted to 12-14 by the addition of about 5 L 30% aqueous NaOH. The phases were separated and the aqueous phase was extracted twice with TBME. The combined organic layers were dried with sodium sulfate and evaporated to give 130 g of a yellow solid that was used further without purification.

Workup

  1. customthe reaction temperature<22° C.
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted twice with TBME
  4. dry with materialThe combined organic layers were dried with sodium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-7c9ad58649224f3dbd34ce78307b90d5
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Reaction notes

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