Sodium hydride → HCID 58443032, compound

HRID 1038972Notes

Reaction equation

HRID 1038972 reaction equation
[C:1]1([C@H:7]([CH2:9][OH:10])[NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].F[C:14]1[CH:15]=[CH:16][C:17]([N+:21]([O-:23])=[O:22])=[C:18]([CH:20]=1)[NH2:19]>CN(C=O)C>[NH2:8][C@H:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:9][O:10][C:14]1[CH:15]=[CH:16][C:17]([N+:21]([O-:23])=[O:22])=[C:18]([CH:20]=1)[NH2:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 753995-Fluoro-2-nitroanilineHCID 2724025(R)-beta-aminophenethyl alcohol

Product 1

HCID 58443032HCID 58443032, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

(R)-(−)-2-Phenylglycinol (5.043 g, 36.8 mmol) was placed in a 250-mL RBF and placed under a nitrogen atmosphere. DMF (100 mL) was added and the reaction was stirred until a clear, colourless solution resulted. NaH (2.206 g, 55.1 mmol) was then added, followed by DMF (10 mL) as a wash, producing a vigorous reaction (gas evolution). The reaction was stirred at room temperature until the gas evolution had subsided, leaving a reddish heterogeneous mixture. 5-Fluoro-2-nitroaniline (6.89 g, 44.1 mmol) was then added, followed by DMF (10 mL), which immediately produced a bright red colour. The reaction was left stirring at room temperature and monitored by LC-MS. The reaction was quenched by its addition to an Erlenmeyer flask containing ethyl acetate (200 mL) and dilute aqueous NaHCO3 (250 mL). The phases were separated in a separatory funnel, and the organic layer was washed with water (150 mL), then brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The reaction was then purified by silica gel column (5-75% EtOAc in n-heptane), yielding two fractions of high purity 5-[(2R)-2-amino-2-phenylethoxy]-2-nitroaniline, both contaminated with residual DMF, as a yellow-orange oil. LRMS (ESI) calc'd for (C14H16N3O3) [M+H]+, 274.1; found 274.1.

Workup

  1. customresulted
  2. customproducing
  3. customa vigorous reaction (gas evolution)
  4. stirringThe reaction was stirred at room temperature until the gas evolution
  5. customleaving a reddish heterogeneous mixture
  6. customimmediately produced a bright red colour
  7. waitThe reaction was left
  8. stirringstirring at room temperature
  9. customThe reaction was quenched by its addition to an Erlenmeyer flask
  10. additioncontaining ethyl acetate (200 mL) and dilute aqueous NaHCO3 (250 mL)
  11. customThe phases were separated in a separatory funnel
  12. washthe organic layer was washed with water (150 mL)
  13. dry with materialbrine (100 mL), dried over anhydrous Na2SO4
  14. concentrationconcentrated in vacuo
  15. customThe reaction was then purified by silica gel column (5-75% EtOAc in n-heptane)

Sources & evidence

ORD record
ord-6ad7ecb5ba354ad4a631622544a0af29
Source dataset
uspto-grants-2013_10
Patent number
US08552019B2

Reaction notes

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