Sodium Methoxide → 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

HRID 930382Notes

Reaction equation

HRID 930382 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH3:27])[CH2:14][C@@H:13]([C:15]([F:18])([F:17])[F:16])[O:12][C:11]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[N:10]2)[C:5](F)=[N:6][CH:7]=1.[CH3:28][O-:29].[Na+]>>[Br:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH3:27])[CH2:14][C@@H:13]([C:15]([F:18])([F:17])[F:16])[O:12][C:11]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[N:10]2)[C:5]([O:29][CH3:28])=[N:6][CH:7]=1

Participants

3

Reactant 2

HCID 10942334Sodium MethoxideHCID 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

Product 1

HCID 86732211tert-Butyl ((4S,6S)-4-(5-bromo-2-methoxypyridin-3-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamateYield 97%

Conditions

Temperature
50 °C

Procedure

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 (5k, 0.500 g, 1.096 mmol, as described in Example 31, Method G, Step 9) was treated with sodium methanolate 25% MeOH (3 mL). The reaction was heated at 50° C. for 40 min. The reaction was quenched with water and methanol was removed by reduced pressure. The resulting mixture was extracted with EtOAc 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 0-30% EtOAc/hexane to give 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 (0.49 g, 97% yield). MS m/z=469.9 [M+H]+. Calculated for C17H21BrF3N3O4: 468.3

Workup

  1. customThe reaction was quenched with water and methanol
  2. customwas removed by reduced pressure
  3. extractionThe resulting mixture was extracted with EtOAc three times
  4. customThe combined organic layers were dried on sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-cee3049363364b429deb19f3c6c968fa
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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