Water → HCID 86732275, compound

HRID 930438Notes

Reaction equation

HRID 930438 reaction equation
O.[Cl:2][C:3]1[C:8]([F:9])=[CH:7][C:6]([N+:10]([O-])=O)=[CH:5][C:4]=1[C@:13]1([CH3:24])[CH2:18][C@@H:17]([C:19]([F:22])([F:21])[F:20])[O:16][C:15]([NH2:23])=[N:14]1.FC(F)(F)C(O)=O>C(O)(=O)C.[Zn]>[NH2:10][C:6]1[CH:7]=[C:8]([F:9])[C:3]([Cl:2])=[C:4]([C@:13]2([CH3:24])[CH2:18][C@@H:17]([C:19]([F:22])([F:21])[F:20])[O:16][C:15]([NH2:23])=[N:14]2)[CH:5]=1

Participants

6

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 86732274HCID 86732274, compound

Product 1

HCID 86732275HCID 86732275, compoundYield 57.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

To a cooled (cold water) solution of (4S,6S)-4-(2-chloro-3-fluoro-5-nitrophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (1.2 g, 3.37 mmol) in acetic acid (14 mL) was added 2,2,2-trifluoroacetic acid (2.00 mL, 27.0 mmol) followed by zinc, dust (1.19 g, 18.22 mmol) in one portion (exothermic). After stirred for 10 min, water bath was removed. The mixture was stirred at ambient temperature for 1.5 hrs and then concentrated. The residue was basified with 1N NaOH. The aqueous layer was extracted three times with DCM. The organic extracts were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude was purified by silica gel chromatography (2-10% MeOH-DCM) to give (4S,6S)-4-(5-amino-2-chloro-3-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine as an off-white solid (0.636 g, 57.9% yield). MS m/z=326 [M+H]+. Calculated for C12H12ClF4N3O: 325.7.

Workup

  1. customwater bath was removed
  2. stirringThe mixture was stirred at ambient temperature for 1.5 hrs
  3. concentrationconcentrated
  4. extractionThe aqueous layer was extracted three times with DCM
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude was purified by silica gel chromatography (2-10% MeOH-DCM)

Sources & evidence

ORD record
ord-c07f976bbbf740d8b2f0c25a041c45a8
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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