Hydroxylamine → 1,1-Dimethylethyl 4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl)-1-piperidinecarboxylate

HRID 1528516Notes

Reaction equation

HRID 1528516 reaction equation
[CH:1]([C:3]1[N:4]=[C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[S:6][CH:7]=1)=O.[NH2:21][OH:22].[CH2:23]=[CH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.Cl[O-].[Na+]>C(O)C.O1CCCC1>[C:25]1([CH:24]2[O:22][N:21]=[C:1]([C:3]3[N:4]=[C:5]([CH:8]4[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]4)[S:6][CH:7]=3)[CH2:23]2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 787HydroxylamineHCID 7501StyreneHCID 7172298tert-Butyl 4-(4-formyl-1,3-thiazol-2-yl)piperidine-1-carboxylateHCID 23665760Sodium Hypochlorite

Product 1

HCID 666187381,1-Dimethylethyl 4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl)-1-piperidinecarboxylateYield 43.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 1,1-dimethylethyl 4-(4-formyl-2-thiazolyl)-1-piperidinecarboxylate (1.0 g, 3.4 mmol) in ethanol (5 mL) was added an aqueous solution of hydroxylamine (50 wt. %, 0.25 mL, 4.0 mmol). The reaction mixture was heated at 60° C. for 1 h, during which time the reaction mixture became homogeneous. The resulting solution was cooled to room temperature and diluted with tetrahydrofuran (10 mL). To the reaction mixture was added styrene (0.57 mL, 5 mmol), followed by portionwise addition of Clorox® aqueous sodium hypochlorite solution (10.5 mL) over 3 h. The reaction mixture was stirred overnight at room temperature, and the resulting solid was filtered, washed with water and diethyl ether, and air dried to give the title compound as a white powder (610 mg). The filtrate was diluted with saturated aqueous sodium bicarbonate solution and extracted with diethyl ether. The extract was dried (MgSO4) and concentrated under reduced pressure to give 850 mg of the title compound as a yellow oil. The oil was diluted with diethyl ether (4 mL) and allowed to stand to give additional 233 mg of the product as a white solid.

Workup

  1. temperatureThe resulting solution was cooled to room temperature
  2. filtrationthe resulting solid was filtered
  3. washwashed with water and diethyl ether, and air
  4. customdried

Sources & evidence

ORD record
ord-096779990a95416b8d678aeff2d3d931
Source dataset
uspto-grants-2015_07
Patent number
US09090604B2

Reaction notes

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