Tetrabutylammonium Fluoride → 5-(6-((2R,6S)-2,6-dimethylmorpholino)-7-fluoro-5-(hydroxymethyl)benzo[d]isoxazol-3-yl)-1,3,4-oxadiazol-2(3H)-one

HRID 245454Notes

Reaction equation

HRID 245454 reaction equation
[Si]([O:18][CH2:19][C:20]1[C:21]([N:36]2[CH2:41][C@H:40]([CH3:42])[O:39][C@H:38]([CH3:43])[CH2:37]2)=[C:22]([F:35])[C:23]2[O:27][N:26]=[C:25]([C:28]3[O:32][C:31](=[O:33])[NH:30][N:29]=3)[C:24]=2[CH:34]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH3:42][C@@H:40]1[CH2:41][N:36]([C:21]2[C:20]([CH2:19][OH:18])=[CH:34][C:24]3[C:25]([C:28]4[O:32][C:31](=[O:33])[NH:30][N:29]=4)=[N:26][O:27][C:23]=3[C:22]=2[F:35])[CH2:37][C@H:38]([CH3:43])[O:39]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 673579695-(5-((tert-butyldiphenylsilyloxy)methyl)-6-((2R,6S)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazol-3-yl)-1,3,4-oxadiazol-2(3H)-one2×

Product 1

HCID 674343045-(6-((2R,6S)-2,6-dimethylmorpholino)-7-fluoro-5-(hydroxymethyl)benzo[d]isoxazol-3-yl)-1,3,4-oxadiazol-2(3H)-oneYield 79.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-(5-((tert-butyldiphenylsilyloxy)methyl)-6-((2R,6S)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazol-3-yl)-1,3,4-oxadiazol-2(3H)-one (Intermediate 208, 490 mg, 0.81 mmol) in 10 ml of THF was treated with TBAF (1M in THF; 1626 μl, 1.63 mmol) at room temperature for 16 hours. Reaction quenched with aq ammonium chloride solution and Extracted with ethyl acetate. Crude product purified on column (50-80% etoac in hexanaes) to give 5-(6-((2R,6S)-2,6-dimethylmorpholino)-7-fluoro-5-(hydroxymethyl)benzo[d]isoxazol-3-yl)-1,3,4-oxadiazol-2(3H)-one (235 mg, 79%)

Workup

  1. customReaction
  2. customquenched with aq ammonium chloride solution
  3. extractionExtracted with ethyl acetate
  4. customCrude product purified on column (50-80% etoac in hexanaes)

Sources & evidence

ORD record
ord-b3ab6c34b5a7440cb7718fcfa1649574
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Reaction notes

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