Sodium hydride → (3-Benzyloxycarbonylamino-2-oxo-2h-pyridin-1-yl)acetic acid tert-butyl ester

HRID 1057754Notes

Reaction equation

HRID 1057754 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11](=[O:20])[NH:12][C:13]1[C:14]([OH:19])=[N:15][CH:16]=[CH:17][CH:18]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>C1COCC1>[C:26]([O:25][C:23](=[O:24])[CH2:22][N:15]1[CH:16]=[CH:17][CH:18]=[C:13]([NH:12][C:11]([O:10][CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[O:20])[C:14]1=[O:19])([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 178522213HCID 178522213, compound

Product 1

HCID 70027044(3-Benzyloxycarbonylamino-2-oxo-2h-pyridin-1-yl)acetic acid tert-butyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.070 g of a 60% suspension in mineral oil, 1.75 mmol, 1.0 equiv) was added to a solution of (2-hydroxypyridin-3-yl)carbamic acid benzyl ester prepared as described in Example 1) (0.415 g, 1.70 mmol, 1 equiv) in THF (20 mL) at 0° C. The reaction mixture was stirred for 20 min at 0° C., then tert-butyl bromoacetate (0.275 mL, 1.86 mmol, 1.1 equiv) was added. The reaction mixture was warmed to 23° C. for 45 min, then was partitioned between 0.5 M HCl (150 mL) and EtOAc (2×100 mL). The organic layers were dried over Na2SO4 and were concentrated. Purification of the residue by flash column chromatography (30% EtOAc in hexanes) provided the title compound (0.485 g, 85%) as an off-white solid: mp=88-90° C.; IR (cm−1) 3380, 1739, 1652, 1604; 1H NMR (CDCl3) δ 1.48 (s, 9H), 4.57 (s, 2H), 5.20 (s, 2H), 6.25 (t, 1H, J=7.1), 6.87 (dd, 1H, J=6.9, 1.7), 7.27-7.41 (m, 5H), 7.86 (s, br, 1H), 8.05 (d, br, 1H J=6.8); Anal. C19H22N2O5: C, H, N.

Workup

  1. customprepared
  2. customat 0° C
  3. temperatureThe reaction mixture was warmed to 23° C. for 45 min
  4. customwas partitioned between 0.5 M HCl (150 mL) and EtOAc (2×100 mL)
  5. dry with materialThe organic layers were dried over Na2SO4
  6. concentrationwere concentrated
  7. customPurification of the residue by flash column chromatography (30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-79ae0c207e254a5b88aa774b14b06495
Source dataset
uspto-grants-2003_02
Patent number
US06514997B2

Reaction notes

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