Sodium hydride → tert-Butyl 4-(2-methyl-2-(4-nitronaphthalen-1-yloxy)propyl)pyridin-2-ylcarbamate

HRID 872413Notes

Reaction equation

HRID 872413 reaction equation
[OH:1][C:2]([CH3:19])([CH3:18])[CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=1.[H-].[Na+].F[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([N+:33]([O-:35])=[O:34])=[CH:25][CH:24]=1>CN(C=O)C>[CH3:18][C:2]([O:1][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([N+:33]([O-:35])=[O:34])=[CH:25][CH:24]=1)([CH3:19])[CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:16])[CH3:15])[CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2617641-Fluoro-4-nitronaphthaleneHCID 58416752tert-Butyl 4-(2-hydroxy-2-methylpropyl)pyridin-2-ylcarbamate

Product 1

HCID 67395048tert-Butyl 4-(2-methyl-2-(4-nitronaphthalen-1-yloxy)propyl)pyridin-2-ylcarbamateYield 16.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl 4-(2-hydroxy-2-methylpropyl)pyridin-2-ylcarbamate (26) (292 mg, 1.10 mmol) in DMF (5.0 mL), at 0° C. under nitrogen, was added sodium hydride (132 mg, 3.29 mmol, 60 wt %). The resulting orange mixture was stirred at 0° C. for 45 min, and then a solution of 1-fluoro-4-nitronaphthalene (210 mg, 1.10 mmol) in DMF (5.0 mL) was added dropwise, over 2 min. The dark-brown mixture was stirred at 0° C. for 5 min, and then at RT. After 90 min, the reaction was quenched by addition of 4.0 mL aqueous NH4Cl solution. Diethyl ether (40 mL), EtOAc (40 mL) and water (40 mL) were added, and the layers separated. The aqueous layer was extracted with a mixture of diethyl ether and EtOAc (1:1, 30 mL×2). The combined organic extracts were washed with brine (50 mL), dried and the solvents removed under reduced pressure. The crude mixture was purified by column chromatography (40 g) eluting with 0 to 70% EtOAc in iso-hexane, to give tert-butyl 4-(2-methyl-2-(4-nitronaphthalen-1-yloxy)propyl)pyridin-2-ylcarbamate (27) (79 mg, 15%) as an orange foam: m/z 438 (M+H)+ (ES+).

Workup

  1. stirringThe dark-brown mixture was stirred at 0° C. for 5 min
  2. customat RT
  3. waitAfter 90 min
  4. customthe reaction was quenched by addition of 4.0 mL aqueous NH4Cl solution
  5. additionDiethyl ether (40 mL), EtOAc (40 mL) and water (40 mL) were added
  6. customthe layers separated
  7. extractionThe aqueous layer was extracted with a mixture of diethyl ether and EtOAc (1:1, 30 mL×2)
  8. washThe combined organic extracts were washed with brine (50 mL)
  9. customdried
  10. customthe solvents removed under reduced pressure
  11. customThe crude mixture was purified by column chromatography (40 g)
  12. washeluting with 0 to 70% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-964cda84443f4b19ba16e9a2dd7f054f
Source dataset
uspto-grants-2015_03
Patent number
US08975285B2

Reaction notes

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