Methyl iodide → tert-Butyl (2-chloro-3-methylpyridin-4-yl)carbamate

HRID 551282

Reaction equation

HRID 551282 reaction equation
[C:1]([Li])(C)(C)C.[C:6]([O:10][C:11](=[O:20])[NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([Cl:19])[CH:14]=1)([CH3:9])([CH3:8])[CH3:7].CI>C1COCC1>[C:6]([O:10][C:11](=[O:20])[NH:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([Cl:19])[C:14]=1[CH3:1])([CH3:9])([CH3:7])[CH3:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 21858447tert-butyl N-(2-chloropyridin-4-yl)carbamateHCID 178418306HCID 178418306, compound

Product 1

HCID 70701091tert-Butyl (2-chloro-3-methylpyridin-4-yl)carbamateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

tert-Butyllithium (29 mL of 1.7M in pentane, 50 mmol) was added dropwise to a vigorously stirring solution of (2-chloropyridin-4-yl)carbamic acid tert-butyl ester (4.57 g, 20 mmol) in THF (150 mL) at −78° C. under nitrogen. The reaction mixture was kept at this temperature for 4 hours before adding a solution of methyl iodide (3.41 g, 24 mmol) in THF (20 mL). Warmed the reaction mixture to 0° C. over 2 hours, and quenched the reaction with saturated aqueous ammonium chloride solution (100 mL). Extracted into ethyl acetate, washed with brine, dried over magnesium sulfate, and concentrated to dryness. Flash column chromatography on silica gel gave the product as a white solid (2.93 g, 12 mmol). 1H NMR (CDCl3) δ 8.11 (d, 1H), 7.98 (d, 1H), 6.58 (br s, 1H), 2.30 (s, 3H), 1.52 (s, 9H). ESI MS (M+1)+: 243, 245 (Cl).

Workup

  1. customquenched
  2. customthe reaction with saturated aqueous ammonium chloride solution (100 mL)
  3. extractionExtracted into ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-77e873a74d9c42d9996d0f4840bf29c3
Source dataset
uspto-grants-2011_05
Patent number
US07947684B2

Linked notes

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