Dimethylformamide → 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

HRID 1746138Notes

Reaction equation

HRID 1746138 reaction equation
O1[CH:5]=[CH:4][CH2:3][NH:2]1.[Cl-].[NH4+:7].[N-:8]=[N+:9]=[N-:10].[Na+].[C:12]([O:15][CH2:16][CH3:17])(=O)[CH3:13].[CH3:18][N:19](C)[CH:20]=[O:21]>O>[N:2]1[CH:3]=[CH:4][CH:5]=[C:12]([O:15][C:16]2[CH2:17][CH2:20][O:21][N:7]=2)[CH:13]=1.[NH:8]1[CH:18]=[N:19][N:10]=[N:9]1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 193504172,3-Dihydro-1,2-oxazole

Product 2

HCID 668185323-(Pyridin-3-yloxy)-4,5-dihydroisoxazoleHCID 178418441HCID 178418441, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-195a and I-195b were prepared according to the following procedure: racemic dihydroisoxazole I-178 (1.0 equiv) was dissolved in N,N-dimethylforamide (0.1 M with respect to isoxazole) after which ammonium chloride (3.1 equiv) and sodium azide (1.5 equiv) were added. The reaction was then heated in an oil bath to 120° C. for 4 h after which point it the reaction was transferred to a separatory funnel with excess ethyl acetate and water. The organic layer was washed with water and saturated sodium chloride, dried over sodium sulfate and concentrated to provide a crude oil that was purified by flash silica gel chromatography (hexanes/ethyl acetate) to provide the desired racemic tetrazole I-195. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=393.2 m/z. Activity: A

Workup

  1. additionwere added
  2. washThe organic layer was washed with water and saturated sodium chloride
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customto provide a crude oil that
  6. customwas purified by flash silica gel chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-d996374244ae4ada949a524ababefbee
Source dataset
uspto-grants-2015_10
Patent number
US09149465B2

Reaction notes

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