Sodium hydride → Tert-butyl 4-(4-nitroisothiazol-5-yloxy)piperidine-1-carboxylate

HRID 871036Notes

Reaction equation

HRID 871036 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].Br[C:18]1[S:22][N:21]=[CH:20][C:19]=1[N+:23]([O-:25])=[O:24]>O1CCOCC1.C(OCC)(=O)C>[N+:23]([C:19]1[CH:20]=[N:21][S:22][C:18]=1[O:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)([O-:25])=[O:24]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 126311735-Bromo-4-nitroisothiazole

Product 1

HCID 86720856Tert-butyl 4-(4-nitroisothiazol-5-yloxy)piperidine-1-carboxylateYield 44.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (1B2) (464 mg, 2.3 mmol) in dioxane (10 mL) at room temperature was added NaH (114 mg, 2.8 mmol). The mixture was stirred for 20 min and 5-bromo-4-nitroisothiazole (P) (400 mg, 1.9 mmol) was added. The mixture was stirred at 65° C. for 5 hours, cooled to room temperature, diluted with ethyl acetate (100 mL), washed with brine, dried over Na2SO4, and concentrated in vacuo at room temperature (25° C.). The residue was purified with flash column (eluent: 10-30% ethyl acetate/petroleum ether) to afford the product tert-butyl 4-(4-nitroisothiazol-5-yloxy)piperidine-1-carboxylate (1C3) (280 mg, 0.85 mmol).

Workup

  1. stirringThe mixture was stirred at 65° C. for 5 hours
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo at room temperature (25° C.)
  5. customThe residue was purified with flash column (eluent: 10-30% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-ece71a9fb14849f8a2ed509b4c8e198e
Source dataset
uspto-grants-2015_03
Patent number
US08969584B2

Reaction notes

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