Hydrochloric Acid → (6-((2R,6S)-2,6-dimethylmorpholino)-7-fluoro-3-methylbenzo[d]isoxazol-5-yl)methanol

HRID 245370Notes

Reaction equation

HRID 245370 reaction equation
[Si]([O:18][CH2:19][C:20]1[C:21]([N:35]2[CH2:40][C@H:39]([CH3:41])[O:38][C@H:37]([CH3:42])[CH2:36]2)=[C:22]([F:34])[C:23]([O:29][N:30]=C(C)C)=[C:24]([C:26](=O)[CH3:27])[CH:25]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.Cl>C(O)C>[CH3:42][C@@H:37]1[CH2:36][N:35]([C:21]2[C:20]([CH2:19][OH:18])=[CH:25][C:24]3[C:26]([CH3:27])=[N:30][O:29][C:23]=3[C:22]=2[F:34])[CH2:40][C@H:39]([CH3:41])[O:38]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 866580551-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-3-fluoro-2-(propan-2-ylideneaminooxy)phenyl)ethanone

Product 1

HCID 67358969(6-((2R,6S)-2,6-dimethylmorpholino)-7-fluoro-3-methylbenzo[d]isoxazol-5-yl)methanolYield 39%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of 1-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-3-fluoro-2-(propan-2-ylideneaminooxy)phenyl)ethanone (Intermediate 32, 77 mg, 0.13 mmol, crude reaction product from above reaction) dissolved in ethanol (5 ml) was treated with 5 ml of 5% aqueous HCl at 75° C. for 2 hours. Reaction quenched with 10% aqueous sodium bicarbonate solution and extracted with EtOAc. The organic layer washed with water, dried, and concentrated. The residue purified over a silica gel flash coulmn (elution with 50-70% EtOAc in hexanes) to give the title compound (15 mg, 39%).

Workup

  1. customfrom above reaction)
  2. customReaction
  3. customquenched with 10% aqueous sodium bicarbonate solution
  4. extractionextracted with EtOAc
  5. washThe organic layer washed with water
  6. customdried
  7. concentrationconcentrated
  8. customThe residue purified over a silica gel flash coulmn
  9. wash(elution with 50-70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-104924e427e44e2baf86cc5b94084088
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Reaction notes

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