Formaldehyde → 8-bromo-3,6-di-tert-butyl-3,4-dihydro-2H-benzo[e][1,3]oxazine

HRID 1854165Notes

Reaction equation

HRID 1854165 reaction equation
[CH2:1]=[O:2].[C:3]([NH2:7])([CH3:6])([CH3:5])[CH3:4].[Br:8][C:9]1[CH:14]=[C:13]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:12]=[CH:11][C:10]=1O.[CH:20](O)(C)C>>[Br:8][C:9]1[C:10]2[O:2][CH2:1][N:7]([C:3]([CH3:6])([CH3:5])[CH3:4])[CH2:20][C:11]=2[CH:12]=[C:13]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:14]=1

Participants

5

Reactant 4

HCID 712FormaldehydeHCID 3776Isopropanol2×HCID 6385Tert-ButylamineHCID 751472-Bromo-4-tert-butylphenol

Product 1

HCID 867185598-bromo-3,6-di-tert-butyl-3,4-dihydro-2H-benzo[e][1,3]oxazineYield 85%

Procedure

A mixture of paraformaldehyde (19.99 g, 0.666 mol) and tert-butylamine (70.26 mL, 0.666 mol) in isopropanol (260 mL) was heated to gentle reflux under nitrogen for 75 minutes. A solution of 2-bromo-4-(tert-butyl)phenol (30.5 g, 0.133 mol) in isopropanol (40 mL) was then added and the mixture refluxed for a further 20 hours. The cooled reaction mixture was then concentrated to afford a yellow solid. The crude product was re-crystallized from methanol (100 mL) to give 8-bromo-3,6-di-tert-butyl-3,4-dihydro-2H-benzo[e][1,3]oxazine (36.74 g, 85% yield) as a cream crystalline solid.

Workup

  1. temperaturewas heated
  2. temperatureto gentle reflux under nitrogen for 75 minutes
  3. temperaturethe mixture refluxed for a further 20 hours
  4. customThe cooled reaction mixture
  5. concentrationwas then concentrated
  6. customto afford a yellow solid
  7. customThe crude product was re-crystallized from methanol (100 mL)

Sources & evidence

ORD record
ord-a8a2e5e87aae48838e1fd9f9458162e4
Source dataset
uspto-grants-2015_02
Patent number
US08962657B2

Reaction notes

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