Sodium hydride → Methyl 2-[(5-bromopyridin-2-yl)[(tert-butoxy)carbonyl]amino]acetate

HRID 18250Notes

Reaction equation

HRID 18250 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[N:6][CH:7]=1.[H-].[Na+].Br[CH2:19][C:20]([O:22][CH3:23])=[O:21]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:19][C:20]([O:22][CH3:23])=[O:21])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 162178432-(Boc-amino)-5-bromopyridine

Product 1

HCID 22139000Methyl 2-[(5-bromopyridin-2-yl)[(tert-butoxy)carbonyl]amino]acetateYield 52.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromo-2-(tert-butoxycarbonyl)aminopyridine (25.0 g, 91.5 mmole) in DMF (400 mL) was added portionwise with stirring a 60% dispersion of NaH in mineral oil (4.0 g, 100 mmole). The reaction was stirred for 15 min, then methyl bromoacetate (15 mL, 158.5 mmole) was added dropwise over 15 min. After stirring for 18 h at room temperature the reaction was concentrated to dryness. The remaining residue was taken up in EtOAc (200 mL) and H2O (200 mL) and filtered to remove insoluble material. The EtOAc phase was separated, washed with brine, dried (Na2SO4) and concentrated to dryness. Purification by flash chromatography on silica gel (10% EtOAc/Hexane) gave the title compound (16.56 g, 50%): 1H NMR (400 MHz, CDCl3) δ 8.33 (s, 1 H), 7.73 (d, J=2.5 Hz, 1 H), 7.71 (d, J=2.5 Hz, 1 H), 4.69 (s, 2 H), 3.75 (s, 3 H), 1.51 (s, 9 H).

Workup

  1. stirringAfter stirring for 18 h at room temperature the reaction
  2. concentrationwas concentrated to dryness
  3. filtrationH2O (200 mL) and filtered
  4. customto remove insoluble material
  5. customThe EtOAc phase was separated
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customPurification by flash chromatography on silica gel (10% EtOAc/Hexane)

Sources & evidence

ORD record
ord-6090999cde3f48c8b52fce72a9670085
Source dataset
uspto-grants-2010_06
Patent number
US07741339B2

Reaction notes

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