Water → 3-(3,3-Difluoroazetidine-1-carbonyl)-6,7-difluorobenzo[d]isoxazole-5-carbaldehyde

HRID 577940Notes

Reaction equation

HRID 577940 reaction equation
[F:1][C:2]1([F:24])[CH2:5][N:4]([C:6]([C:8]2[C:12]3[CH:13]=[C:14]([CH:19](OC)[O:20]C)[C:15]([F:18])=[C:16]([F:17])[C:11]=3[O:10][N:9]=2)=[O:7])[CH2:3]1.O>C1COCC1.C(OCC)(=O)C>[F:24][C:2]1([F:1])[CH2:3][N:4]([C:6]([C:8]2[C:12]3[CH:13]=[C:14]([CH:19]=[O:20])[C:15]([F:18])=[C:16]([F:17])[C:11]=3[O:10][N:9]=2)=[O:7])[CH2:5]1

Participants

5

Reactant 2

HCID 962WaterHCID 67358946(3,3-Difluoroazetidin-1-yl)(5-(dimethoxymethyl)-6,7-difluorobenzo[d]isoxazol-3-yl)methanone2×

Product 1

HCID 866580973-(3,3-Difluoroazetidine-1-carbonyl)-6,7-difluorobenzo[d]isoxazole-5-carbaldehydeYield 92.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3,3-Difluoroazetidin-1-yl)(5-(dimethoxymethyl)-6,7-difluorobenzo[d]isoxazol-3-yl)methanone (Intermediate 228, 3.336 g, 9.58 mmol) was dissolved in a 4:1 THF:water mixture (62.5 ml) and heated at 75° C. with tosic acid monohydrate (0.911 g, 4.79 mmol) for three hours. The reaction was allowed to cool to room temperature, diluted with ethyl acetate, washed 3× with saturated NaHCO3, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography using a gradient of hexanes to ethyl acetate. Fractions were combined and concentrated to give the title compound (2.66 g, 8.83 mmol).

Workup

  1. washwashed 3× with saturated NaHCO3
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel column chromatography
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-96998b27304b4d8abe2fc0a7e2f0d726
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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