Pyridine → 1-{5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorophenyl}-2,2,2-trifluoro-N-hydroxyethanimine

HRID 577903Notes

Reaction equation

HRID 577903 reaction equation
N1C=CC=CC=1.[Si:7]([O:24][CH2:25][C:26]1[C:27]([N:40]2[CH2:45][C@H:44]([CH3:46])[O:43][C@H:42]([CH3:47])[CH2:41]2)=[C:28]([F:39])[C:29]([F:38])=[C:30]([C:32](=O)[C:33]([F:36])([F:35])[F:34])[CH:31]=1)([C:20]([CH3:23])([CH3:22])[CH3:21])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Cl.[NH2:49][OH:50]>C(O)C>[Si:7]([O:24][CH2:25][C:26]1[C:27]([N:40]2[CH2:41][C@H:42]([CH3:47])[O:43][C@H:44]([CH3:46])[CH2:45]2)=[C:28]([F:39])[C:29]([F:38])=[C:30]([C:32](=[N:49][OH:50])[C:33]([F:36])([F:35])[F:34])[CH:31]=1)([C:20]([CH3:21])([CH3:23])[CH3:22])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 866580921-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2,2,2-trifluoroethanone2×

Product 1

HCID 866580911-{5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorophenyl}-2,2,2-trifluoro-N-hydroxyethanimineYield 100.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Pyridine (2597 μl, 32.11 mmol) was added to a mixture of 1-(5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6S)-2,6-dimethylmorpholino)-2,3-difluorophenyl)-2,2,2-trifluoroethanone (Intermediate 130, 1900 mg, 3.21 mmol) and hydroxylamine hydrochloride (223 mg, 3.21 mmol) in 50 ml of ethanol and the solution was heated at 80° C. for 40 hours. The reaction mixture was concentrated, diluted with water, and extracted with ethyl acetate. The organic phases were combined, dried (Na2SO4), and concentrated to give the crude title compound (1.95 g, 98%), which was used in the next step without further purification.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water
  3. extractionextracted with ethyl acetate
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-049607b4b2e445a895b93889ead84396
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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