6'-Bromo-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-amine → (4'R)-6'-bromo-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-amine

HRID 594915Notes

Reaction equation

HRID 594915 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:13]3([CH2:17][O:16][C:15]([NH2:18])=[N:14]3)[C:10]3([CH2:12][CH2:11]3)[C:9]([CH3:20])([CH3:19])[O:8][C:5]2=[CH:6][CH:7]=1.O.C([C@](C(O)=O)(O)[C@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1>CO>[Br:1][C:2]1[CH:3]=[C:4]2[C@@:13]3([CH2:17][O:16][C:15]([NH2:18])=[N:14]3)[C:10]3([CH2:12][CH2:11]3)[C:9]([CH3:20])([CH3:19])[O:8][C:5]2=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 867243196'-Bromo-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-amineHCID 122598382Dibezoyl-D-tartaric acid monohydrate

Product 1

HCID 86724276(4'R)-6'-bromo-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-amineYield 40.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 6′-bromo-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-amine (3.7 g, 11 mmol) in methanol (50 ml) was added (+)-dibenzoyl-D-tartaric acid monohydrate (4.1 g, 11 mmol). The mixture was stirred at room temperature for 5 minutes and concentrated in vacuo. To the residue was added dioxane (25 ml). The mixture was heated under reflux for 5 minutes, cooled to room temperature and stirred at room temperature overnight. The resulting precipitate was collected, washed with dioxane, and dried in vacuo. The resulting powder was dissolved in saturated aqueous sodium hydrogen carbonate and chloroform. The mixture was extracted with chloroform, and the organic layer was dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford (4′R)-6′-bromo-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-amine (1.5 g). The mother liquor was concentrated in vacuo and purified by NH-silica gel column chromatography (CHCl3/MeOH=20:1). The purified material was treated with (−)-dibenzoyl-L-tartaric acid monohydrate (2.0 g, 5.4 mmol) in the same manner as described above which lead to isolation of (4′S)-6′-bromo-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-amine (1.2 g).

Workup

  1. concentrationconcentrated in vacuo
  2. additionTo the residue was added dioxane (25 ml)
  3. temperatureThe mixture was heated
  4. temperatureunder reflux for 5 minutes
  5. temperaturecooled to room temperature
  6. stirringstirred at room temperature overnight
  7. customThe resulting precipitate was collected
  8. washwashed with dioxane
  9. customdried in vacuo
  10. dissolutionThe resulting powder was dissolved in saturated aqueous sodium hydrogen carbonate
  11. extractionThe mixture was extracted with chloroform
  12. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-303b261359df4d0b8c921f92fe4e91a7
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Reaction notes

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