Sodium hydride → (R)-tert-butyl-2-((2-cyano-3-nitrophenoxy)methyl)piperidine-1-carboxylate

HRID 1483954Notes

Reaction equation

HRID 1483954 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:14][OH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+:16]([C:19]1[CH:26]=[CH:25][CH:24]=[C:23]([N+]([O-])=O)[C:20]=1[C:21]#[N:22])([O-:18])=[O:17].[H-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:14][O:15][C:23]1[CH:24]=[CH:25][CH:26]=[C:19]([N+:16]([O-:18])=[O:17])[C:20]=1[C:21]#[N:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 520718DinitrobenzonitrileHCID 6933953tert-butyl (2R)-2-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 86714287(R)-tert-butyl-2-((2-cyano-3-nitrophenoxy)methyl)piperidine-1-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-tert-butyl-2-(hydroxymethyl)piperidine-1-carboxylate (Example 15f, 7.10 g, 33.0 mmol) and 2,6-dinitrobenzonitrile (6.37 g, 33.0 mmol) in THF (142 mL) cooled to −78° C., was added NaH (60% dispersion in oil, 1.45 g, 36.3 mmol). The reaction was allowed to warm to room temperature and stirring was continued for 18 hours. Upon completion, the reaction was cooled to 0° C. and quenched with water. The mixture was extracted with ethyl acetate, and the organic extracts were combined and dried over anhydrous Na2SO4, filtered, and concentrated. The residue was recrystallized from ethyl acetate/hexanes to afford (R)-tert-butyl-2-((2-cyano-3-nitrophenoxy)methyl)piperidine-1-carboxylate (10.8 g, 91%) as a yellow solid. MS 282 (MH+-boc).

Workup

  1. temperatureUpon completion, the reaction was cooled to 0° C.
  2. customquenched with water
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-235f464ef04d4bda97065f6a5d075437
Source dataset
uspto-grants-2016_08
Patent number
US09420814B2

Reaction notes

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