Trifluoroacetic acid → (4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

HRID 930383Notes

Reaction equation

HRID 930383 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@:10]2([CH3:28])[CH2:15][C@@H:14]([C:16]([F:19])([F:18])[F:17])[O:13][C:12]([NH:20]C(=O)OC(C)(C)C)=[N:11]2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.FC(F)(F)C(O)=O>>[Br:1][C:2]1[CH:3]=[C:4]([C@:10]2([CH3:28])[CH2:15][C@@H:14]([C:16]([F:18])([F:19])[F:17])[O:13][C:12]([NH2:20])=[N:11]2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86732211tert-Butyl ((4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate

Product 1

HCID 86732212(4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amineYield 83.1%

Procedure

tert-Butyl ((4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate (0.56 g, 1.196 mmol) was treated with trifluoroacetic acid, 99% (10 ml, 135 mmol) and the mixture was stirred at room temperature for 15 min. The solvent was removed and the residue was worked up with saturated sodium bicarbonate solution and extracted with dichloromethane three times. The combined organic layers were dried on sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography using a gradient of 10-60% EtOAc/hexane to give (4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.366 g, 0.994 mmol, 83% yield).

Workup

  1. customThe solvent was removed
  2. extractionextracted with dichloromethane three times
  3. customThe combined organic layers were dried on sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-1ffa701ff67d4e19b9ddc45add725488
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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