Dimethyl Carbonate → Methyl N-(4-methylpyridin-3-yl)carbamate

HRID 1257624

Reaction equation

HRID 1257624 reaction equation
CC(C)([O-])C.[K+].[NH2:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1[CH3:14].[C:15](=O)([O:18]C)[O:16][CH3:17]>C1COCC1>[CH3:17][O:16][C:15](=[O:18])[NH:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1[CH3:14]

Participants

5

Reactant 3

HCID 12021Dimethyl CarbonateHCID 1379353-Amino-4-picolineHCID 23665647Potassium tert-butoxide

Product 1

HCID 11672725Methyl N-(4-methylpyridin-3-yl)carbamateYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of potassium tert-butoxide (32.8 g, 277 mmol) in THF (250 mL) at 0° C. was treated with 3-amino-4-methylpyridine (10.0 g, 92.5 mmol) and the resulting mixture stirred for 30 minutes before dimethyl carbonate (11.7 mL, 139 mmol) was added. The mixture was stirred for 30 minutes then quenched with water and extracted with ethyl acetate. The combined organic phases were washed with brine then dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (DCM) then triturated with diethyl ether to afford 9.42 g (62%) of (4-methyl-pyridin-3-yl)-carbamic acid methyl ester. LCMS (Method B, ESI): RT=0.40 min, m+H=167.4; 1H NMR (400 MHz, CDCl3) δ: 8.86 (s, 1H), 8.28 (d, 1H), 7.12-7.12 (m, 1H), 6.45 (s, 1H), 3.80 (s, 3H), 2.28 (s, 3H).

Workup

  1. additionwas added
  2. customthen quenched with water
  3. extractionextracted with ethyl acetate
  4. washThe combined organic phases were washed with brine
  5. dry with materialthen dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe resulting residue was purified by column chromatography on silica gel (DCM)
  8. customthen triturated with diethyl ether

Sources & evidence

ORD record
ord-9d5cd1ef7c374d5e89d959be79315aa3
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Linked notes

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