Dimethylformamide → 5-(tert-Butoxy)picolinonitrile

HRID 1405397Notes

Reaction equation

HRID 1405397 reaction equation
[CH3:1][C:2]([O-:5])([CH3:4])[CH3:3].[Na+].CN(C=O)C.F[C:13]1[CH:14]=[CH:15][C:16]([C:19]#[N:20])=[N:17][CH:18]=1>CN(P(N(C)C)(N(C)C)=O)C.O>[C:2]([O:5][C:13]1[CH:14]=[CH:15][C:16]([C:19]#[N:20])=[N:17][CH:18]=1)([CH3:4])([CH3:3])[CH3:1]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 113324532-Cyano-5-fluoropyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 681535125-(tert-Butoxy)picolinonitrileYield 62.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

To NaOtBu (1.57 g, 16.4 mmol) in HMPA (6 mL) was added DMF (6 mL) (to facilitate stirring). 5-Fluoropyridine-2-carbonitrile (1.00 g, 8.19 mmol) was added and the dark mixture was stirred overnight. The mixture was diluted with water (100 mL), extracted with DCM (3×50 mL) and the organics were washed with water (50 mL) and sat. aq. NaHCO3 (50 mL), dried over MgSO4, evaporated and purified by column chromatography (0-50% EtOAc/hex) to give 5-tert-butoxypyridine-2-carbonitrile (0.90 g, 62%) as a yellow solid. ESI-MS m/z calc. 211.1, found 211.9 (M+1)+; Retention time: 0.97 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, J=2.7, 0.5 Hz, 1H), 7.67-7.56 (m, 1H), 7.41-7.31 (m, 1H), 1.52-1.38 (m, 10H).

Workup

  1. extractionextracted with DCM (3×50 mL)
  2. washthe organics were washed with water (50 mL) and sat. aq. NaHCO3 (50 mL)
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. custompurified by column chromatography (0-50% EtOAc/hex)

Sources & evidence

ORD record
ord-b0df312b47ca48349e70856adc8fbb58
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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