Water → HCID 67168993, compound

HRID 1506467Notes

Reaction equation

HRID 1506467 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3CCOCC3)=[CH:7][CH2:8][N:9]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:32]1([C:38]2[C:42]([C:43]([F:46])([F:45])[F:44])=[C:41]([C:47](F)=[O:48])[O:40][N:39]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.Cl.NO.C([O-])(=[O:55])C.[Na+].O>C(#N)C.ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH:7]([C:47]([OH:48])([C:41]4[O:40][N:39]=[C:38]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[C:42]=4[C:43]([F:46])([F:45])[F:44])[O:55][N:19]=3)[CH2:8][N:9]([C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])[C:10]=2[CH:11]=1

Participants

9

Reactant 6

HCID 962WaterHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 58374067HCID 58374067, compoundHCID 67171234HCID 67171234, compound

Product 1

HCID 67168993HCID 67168993, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a homogeneous solution of tert-butyl 7-bromo-4-morpholinoquinoline-1(2H)-carboxylate (Preparation 77A, 0.598 g, 1.513 mmol) and triethylamine (0.419 mL, 3.03 mmol) in acetonitrile (20 mL) at 0° C. was added a solution of 3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl fluoride (I-4, 0.392 g, 1.51 mmol) in acetonitrile (1.0 mL). The reaction mixture was stirred at 0° C. for 2.5 hours and then overnight at room temperature. A homogeneous solution of hydroxylamine hydrochloride (0.421 g, 6.05 mmol) and sodium acetate (0.496 g, 6.05 mmol) in water (0.981 mL, 54.5 mmol) was added, and the reaction mixture was heated at 45° C. for 60 min. The reaction mixture was diluted with dichloromethane, washed with water, and dried over anhydrous sodium sulfate. Concentration under vacuum afforded the crude product which was chromatographed using silica gel chromatography eluting with a 10% mixture of ethyl acetate in hexane to give tert-butyl 7-bromo-3-hydroxy-3-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-3a,4-dihydroisoxazolo[4,3-c]quinoline-5(3H)-carboxylate (0.050 g, 0.086 mmol, 6% yield) as a yellowish solid. The product had LC/MS M+1=636.2 and 637.2.

Workup

  1. customovernight
  2. customat room temperature
  3. temperaturethe reaction mixture was heated at 45° C. for 60 min
  4. washwashed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationConcentration under vacuum
  7. customafforded the crude product which
  8. customwas chromatographed
  9. washeluting with a 10% mixture of ethyl acetate in hexane

Sources & evidence

ORD record
ord-d1fec1cf0a0a46d796ad91533dd01cdc
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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