Sodium hydride → HCID 58532561, compound

HRID 2069053Notes

Reaction equation

HRID 2069053 reaction equation
[H-].[Na+].[OH:3][CH:4]([CH3:20])[CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:7]=1.F[C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]([N+:32]([O-:34])=[O:33])=[CH:24][CH:23]=1.[NH4+].[Cl-]>CN(C=O)C>[N+:32]([C:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:22]([O:3][CH:4]([CH3:20])[CH2:5][C:6]2[CH:11]=[CH:10][N:9]=[C:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])[CH:7]=2)=[CH:23][CH:24]=1)([O-:34])=[O:33]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2617641-Fluoro-4-nitronaphthaleneHCID 58532570HCID 58532570, compound

Product 1

HCID 58532561HCID 58532561, compoundYield 69.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (119 mg, 2.97 mmol) was added to a stirred solution of tert-butyl 4-(2-hydroxypropyl)pyridin-2-ylcarbamate (47) (250 mg, 0.991 mmol) in DMF (6 mL) at 0° C., under nitrogen and after 45 min a solution of 1-fluoro-4-nitronaphthalene (14) (189 mg, 0.991 mmol) in DMF (6 mL) was added dropwise, over 2 min. The resulting dark-brown reaction mixture was stirred at 0° C. for 5 min, and was then warmed to RT. After 70 min, a saturated aqueous solution of NH4Cl (3 mL) was added and the mixture was partitioned between water and EtOAc. The aqueous layer was extracted twice with EtOAc and the combined organic extracts were washed with brine, dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g; 0-70% EtOAc in isohexane, gradient elution) to afford the title compound (48) (293 mg, 65%) as an orange foam: m/z 424.0 (M+H)+ (ES+).

Workup

  1. additionwas added dropwise, over 2 min
  2. temperaturewas then warmed to RT
  3. waitAfter 70 min
  4. customthe mixture was partitioned between water and EtOAc
  5. extractionThe aqueous layer was extracted twice with EtOAc
  6. washthe combined organic extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe residue was purified by flash column chromatography (SiO2, 40 g; 0-70% EtOAc in isohexane, gradient elution)

Sources & evidence

ORD record
ord-f50a1ea338364bf999e50ea982c5a34e
Source dataset
uspto-grants-2012_10
Patent number
US08299073B2

Reaction notes

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