tert-Butyl chloroacetate → Tert-butyl 2-(6-methoxy-5-methyl-3-nitropyridin-2-yl)acetate

HRID 386499Notes

Reaction equation

HRID 386499 reaction equation
[CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]([N+:10]([O-:12])=[O:11])=[CH:5][N:4]=1.Cl[CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].CC(C)([O-])C.[K+]>C1COCC1>[CH3:1][O:2][C:3]1[N:4]=[C:5]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:6]([N+:10]([O-:12])=[O:11])=[CH:7][C:8]=1[CH3:9]

Participants

5

Reactant 3

HCID 66052tert-Butyl chloroacetateHCID 23665647Potassium tert-butoxideHCID 407869042-Methoxy-3-methyl-5-nitropyridine

Product 1

HCID 44596705Tert-butyl 2-(6-methoxy-5-methyl-3-nitropyridin-2-yl)acetateYield 72.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

A yellow solution of 2-methoxy-3-methyl-5-nitropyridine (68.8 g, 409 mmol) and tert-butyl 2-chloroacetate (77.0 g, 511 mmol) in THF (1 L) was stirred and cooled to −20° C. in a dry ice/isopropanol bath. Potassium tert-butoxide (115 g, 1.02 mol) was added at a rate so that the reaction temperature was less than −10° C. The reaction mixture turned dark purple. When the addition was complete, the cooling bath was removed and the reaction was stirred for 30 min. The stirred reaction mixture was quenched with HCl (500 mL, 2.4 N). The purple solution turned pale yellow and the mixture separated into two layers. The organic layer was separated, washed three times with brine, and concentrated in vacuo. Hexane was added to the amber residue. The mixture was concentrated in vacuo and then dried under high vacuum for 1 hr to give tert-butyl 2-(6-methoxy-5-methyl-3-nitropyridin-2-yl)acetate (83.4 g, 72% yield) as a tan solid: 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 4.09 (s, 2H), 4.02 (s, 2H), 2.21 (s, 3H), 1.44 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 168.81, 163.63, 147.88, 139.41, 135.19, 120.82, 81.66, 54.69, 44.48, 28.03, 15.27. An analytical sample was recrystallized from hexane to give white needles, mp 71-72.5° C. Anal. calcd. for C13H18N2O5: C, 55.31; H, 6.42; N, 9.92. Found: C, 55.52; H, 6.40; N, 9.84.

Workup

  1. customwas less than −10° C
  2. additionWhen the addition
  3. customthe cooling bath was removed
  4. customThe stirred reaction mixture
  5. customwas quenched with HCl (500 mL, 2.4 N)
  6. customthe mixture separated into two layers
  7. customThe organic layer was separated
  8. washwashed three times with brine
  9. concentrationconcentrated in vacuo
  10. additionHexane was added to the amber residue
  11. concentrationThe mixture was concentrated in vacuo
  12. customdried under high vacuum for 1 hr

Sources & evidence

ORD record
ord-7cb6e35338d54ba7aab6801da9a96646
Source dataset
uspto-grants-2013_02
Patent number
US08372847B2

Reaction notes

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