Hydrochloric Acid → (4S,6S)-4-(5-bromo-2-fluoropyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930301Notes

Reaction equation

HRID 930301 reaction equation
C([N:9]([C:17]1[O:18][C@H:19]([C:32]([F:35])([F:34])[F:33])[CH2:20][C@:21]([C:24]2[C:25]([F:31])=[N:26][CH:27]=[C:28]([Br:30])[CH:29]=2)([CH3:23])[N:22]=1)C(=O)OC(C)(C)C)(=O)C1C=CC=CC=1.Cl>CO>[Br:30][C:28]1[CH:29]=[C:24]([C@:21]2([CH3:23])[CH2:20][C@@H:19]([C:32]([F:33])([F:34])[F:35])[O:18][C:17]([NH2:9])=[N:22]2)[C:25]([F:31])=[N:26][CH:27]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86732129tert-Butyl benzoyl((4S,6S)-4-(5-bromo-2-fluoropyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate

Product 1

HCID 86732132(4S,6S)-4-(5-bromo-2-fluoropyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amineYield 65.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The crude product (5k) from step 8 was dissolved in MeOH (5 mL). To this solution was added hydrogen chloride (4M in 1,4-dioxane; 8.0 mL, 32.0 mmol) and the reaction mixture was stirred at room temperature for 14 hours and was heated subsequently to 55° C. for 3.5 hours. The reaction mixture was concentrated, the residue was dissolved in water and the pH was adjusted to neutral with saturated sodium bicarbonate. The solution was extracted with DCM. The combined organic extracts were washed with brine and dried over sodium sulfate. The filtrate was concentrated and purified by silica gel column (gradient 0-5% MeOH/DCM) to afford the title compound (0.335 g, 0.941 mmol, 65.1% yield) as white solid. MS m/z=356, 358 [M]+/[M+2]+. Calculated for C11H10BrFF4N3O: 356.2

Workup

  1. temperaturewas heated subsequently to 55° C. for 3.5 hours
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in water
  4. extractionThe solution was extracted with DCM
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe filtrate was concentrated
  8. custompurified by silica gel column (gradient 0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-f11ff79a0db84a19a78668fe974f46a5
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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