Diisopropylethylamine → 3-(3,3-difluoroazetidine-1-carbonyl)-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde

HRID 577941Notes

Reaction equation

HRID 577941 reaction equation
C(N(C(C)C)CC)(C)C.[CH3:10][C@H:11]1[O:16][C@H:15]([CH3:17])[CH2:14][NH:13][CH2:12]1.[F:18][C:19]1([F:38])[CH2:22][N:21]([C:23]([C:25]2[C:29]3[CH:30]=[C:31]([CH:36]=[O:37])[C:32](F)=[C:33]([F:34])[C:28]=3[O:27][N:26]=2)=[O:24])[CH2:20]1>C(#N)C.O.[Cl-].[Na+].O>[F:38][C:19]1([F:18])[CH2:20][N:21]([C:23]([C:25]2[C:29]3[CH:30]=[C:31]([CH:36]=[O:37])[C:32]([N:13]4[CH2:14][C@@H:15]([CH3:17])[O:16][C@H:11]([CH3:10])[CH2:12]4)=[C:33]([F:34])[C:28]=3[O:27][N:26]=2)=[O:24])[CH2:22]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 11137133trans-2,6-DimethylmorpholineHCID 866580973-(3,3-Difluoroazetidine-1-carbonyl)-6,7-difluorobenzo[d]isoxazole-5-carbaldehyde2×

Product 1

HCID 866580983-(3,3-difluoroazetidine-1-carbonyl)-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Diisopropylethylamine (1.432 ml, 8.20 mmol) and (2R,6R)-2,6-dimethylmorpholine (1.027 ml, 8.20 mmol) were added to a solution of 3-(3,3-difluoroazetidine-1-carbonyl)-6,7-difluorobenzo[d]isoxazole-5-carbaldehyde (Intermediate 241, 1.906 g, 6.31 mmol) in acetonitrile (50 ml). The reaction was stirred at reflux for 20 hours. The reaction was cooled to room temp, diluted with water and brine and extracted twice with ethyl acetate. The organic layers were combined, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography using a gradient of DCM to ethyl acetate. Fractions were combined and concentrated to give the title compound.

Workup

  1. temperatureat reflux for 20 hours
  2. extractionextracted twice with ethyl acetate
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-bb33a86647eb4bb2903e5b36ae2f9951
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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