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

HRID 930300Notes

Reaction equation

HRID 930300 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:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=O)C1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>CO>[Br:30][C:28]1[CH:29]=[C:24]([C@:21]2([CH3:23])[CH2:20][C@@H:19]([C:32]([F:34])([F:33])[F:35])[O:18][C:17]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:14])([CH3:13])[CH3:15])=[N:22]2)[C:25]([F:31])=[N:26][CH:27]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 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 86732131tert-Butyl ((4S,6S)-4-(5-bromo-2-fluoropyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The crude product (5i) from step 7 was dissolved in MeOH (15 mL). Potassium carbonate (Aldrich, 0.200 g, 1.445 mmol) was added and the reaction was stirred at room temperature for 40 min. Hydrogen chloride (4M in 1,4-dioxane; 1.1 mL, 4.40 mmol) was added to the reaction mixture and the solvent was removed under the reduced pressure. The residue was diluted with EtOAc and water. The organic layer was washed with brine, and dried over sodium sulfate. The filtrate was concentrated and the residue used in the next step without further purification. MS m/z=400, 402 [M−tBu]+/[M+2−tBu]+; Calculated for C16H18BrF4N0O3: 456.2

Workup

  1. customthe solvent was removed under the reduced pressure
  2. additionThe residue was diluted with EtOAc and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationThe filtrate was concentrated
  6. customthe residue used in the next step without further purification

Sources & evidence

ORD record
ord-a953261741fe48ceaa40ebc056d6010d
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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