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

HRID 221784Notes

Reaction equation

HRID 221784 reaction equation
[F:1][CH:2]([F:17])[C:3]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])[NH:8][C:7](=S)[CH2:6][O:5][CH2:4]1.[NH3:18]>CO>[F:1][CH:2]([F:17])[C:3]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])[CH2:4][O:5][CH2:6][C:7]([NH2:18])=[N:8]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 86650274HCID 86650274, compound

Product 1

HCID 666659065-Difluoromethyl-5-(2-fluoro-phenyl)-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5-Difluoromethyl-5-(2-fluoro-phenyl)-morpholine-3-thione (160 g, 570 mmol) was dissolved in 2.4 L of a NH3 solution 7 mol/L in methanol for 6.5 h and afterwards left standing overnight. The reaction mixture was evaporated and taken up in 2 L 1N aqueous HCl and 2 L TBME. The aqueous phase was washed with TBME and made basic by the addition of 300 ml 30% aqueous NaOH and some ice. The mixture was extracted with DCM three times and the combined organic layers were dried with Na2SO4 and concentrated in vacuo. The title compound was obtained by crystallization from DCM/heptanes (128.45 g).

Workup

  1. waitafterwards left
  2. customThe reaction mixture was evaporated
  3. washThe aqueous phase was washed with TBME
  4. additionmade basic by the addition of 300 ml 30% aqueous NaOH
  5. extractionThe mixture was extracted with DCM three times
  6. dry with materialthe combined organic layers were dried with Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-83593fa090124885ad49f3cc57a77f65
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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