Sodium hydride → tert-Butyl 3-[(4-methyl-5-nitropyridin-2-yl)oxy]pyrrolidine-1-carboxylate

HRID 510493Notes

Reaction equation

HRID 510493 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1.F[C:17]1[CH:22]=[C:21]([CH3:23])[C:20]([N+:24]([O-:26])=[O:25])=[CH:19][N:18]=1>C1COCC1>[CH3:23][C:21]1[C:20]([N+:24]([O-:26])=[O:25])=[CH:19][N:18]=[C:17]([O:3][CH:4]2[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]2)[CH:22]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 27831772-Fluoro-4-methyl-5-nitropyridineHCID 44169391-Boc-3-pyrrolidinol

Product 1

HCID 89561536tert-Butyl 3-[(4-methyl-5-nitropyridin-2-yl)oxy]pyrrolidine-1-carboxylateYield 65.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A suspension of sodium hydride (60% in oil, 11.54 mmol) in THF (2 mL) was added to tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1.59 g, 8.46 mmol) in THF (15 mL) at 0° C. Once the bubbling had subsided, a solution of 2-fluoro-4-methyl-5-nitropyridine (1.2 g, 7.69 mmol) in THF (3 mL) was added over 5 minutes. After 1 h, more sodium hydride (60% in oil, 0.15 g) was added. After a further 1 h, the reaction was quenched with aqueous ammonium chloride solution and extracted with EtOAc (3×20 mL). The combined organic extracts were dried over sodium sulfate and concentrated to give a yellow solid. Purification by column chromatography (silica gel: 100-200 mesh, 1:4 EtOAc:heptane) yielded the title compound (1.62 g, 65%) as a yellow solid. LCMS (ES+) 323.3 (M+H)+, RT 1.71 minutes (method 4).

Workup

  1. waitAfter a further 1 h
  2. customthe reaction was quenched with aqueous ammonium chloride solution
  3. extractionextracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. concentrationconcentrated
  6. customto give a yellow solid
  7. customPurification by column chromatography (silica gel: 100-200 mesh, 1:4 EtOAc:heptane)

Sources & evidence

ORD record
ord-01a0d1ef7f8b4ca1a23d17ca56ae9d6c
Source dataset
uspto-grants-2015_08
Patent number
US09096614B2

Reaction notes

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