Dimethylformamide → HCID 68153512, compound

HRID 72968Notes

Reaction equation

HRID 72968 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 68153512HCID 68153512, compoundYield 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), followed by 5-fluoropyridine-2-carbonitrile (1 g, 8.19 mmol) and the reaction mixture was stirred for 16 hours under an atmosphere of nitrogen. The reaction mixture was diluted with water (100 mL) and extracted with DCM (3×50 mL) and layers were separated. The organics were washed sequentially with water (50 mL) and sat. aq. NaHCO3 solution (50 mL) and the organic layer was separated, dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 0-50% EtOAc/hexanes to give 5-tert-butoxypyridine-2-carbonitrile (0.90 g, 62%) as a yellow solid. ESI-MS m/z calc. 176.0. Found 177.5 (M+1)+; Retention time: 1.3 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). To 5-tert-butoxypyridine-2-carbonitrile (0.75 g, 4.26 mmol) in ethanol (10 mL) was added NaOH (4.3 mL of 5 M, 21.3 mmol) and the reaction mixture was heated at 85° C. for 1 hour. The reaction mixture was cooled, concentrated in vacuo and diluted with ethyl acetate (50 mL). The organic layer was washed with mixture of brine solution (10 mL) and 6N HCl (3 mL). The organic layer was separated, dried over MgSO4 and concentrated in vacuo to give 5-tert-butoxypyridine-2-carboxylic acid (0.82 g, 99%) as a yellow solid. ESI-MS m/z calc. 195.1. Found 196.1 (M+1)+; Retention time: 0.62 minutes (3 min run).

Workup

  1. extractionextracted with DCM (3×50 mL) and layers
  2. customwere separated
  3. washThe organics were washed sequentially with water (50 mL) and sat. aq. NaHCO3 solution (50 mL)
  4. customthe organic layer was separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with 0-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-ecf1f9f48fc54fe28c291eaaebd14a37
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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